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Sample records for human respiratory syncytial

  1. Human Respiratory Syncytial Virus and Human Metapneumovirus

    OpenAIRE

    Luciana Helena Antoniassi da Silva; Fernando Rosado Spilki; Adriana Gut Lopes Riccetto; Emilio Elias Baracat; Clarice Weis Arns

    2009-01-01

    The human respiratory syncytial virus (hRSV) and the human metapneumovírus (hMPV) are main etiological agents of acute respiratory infections (ARI). The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV) is the best characterized agent viral of this group, associated with respiratory diseases in...

  2. Human Respiratory Syncytial Virus and Human Metapneumovirus

    Directory of Open Access Journals (Sweden)

    Luciana Helena Antoniassi da Silva

    2009-08-01

    Full Text Available The human respiratory syncytial virus (hRSV and the human metapneumovírus (hMPV are main etiological agents of acute respiratory infections (ARI. The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV is the best characterized agent viral of this group, associated with respiratory diseases in lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV, which is structurally similar to the hRSV, in genomic organization, viral structure, antigenicity and clinical symptoms.  The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains hRSV, the bovine (bRSV, as well as the ovine and caprine respiratory syncytial virus and pneumonia virus of mice, the second genus Metapneumovirus, consists of avian metapneumovirus (aMPV and human metapneumovirus (hMPV. In this work, we present a brief narrative review of the literature on important aspects of the biology, epidemiology and clinical manifestations of infections by two respiratory viruses.

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

    African Journals Online (AJOL)

    DR. AMINU

    membrane of the eyes, mouth, or nose and possibly through the ... transmembrane anchor near the C terminus. It is cleaved into two ... immunity induced by previous strains (Hall, 2001). Fluctuations in the .... isolation, and other serological techniques. Antigen .... Respiratory syncytial virus in B.N. fields, D.M. Knipe and.

  4. 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

  5. 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 ...

  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. Respiratory Syncytial Virus

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Respiratory Syncytial Virus (RSV) Credit: CDC This is the ... the United States. Why Is the Study of Respiratory Syncytial Virus (RSV) a Priority for NIAID? In ...

  8. 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 ...

  9. 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

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

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Henrik Larsen, Hans; Koch, Anders

    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 respiratory support. hMPV is present in young...

  11. Transmission of human respiratory syncytial virus in the immunocompromised ferret model

    NARCIS (Netherlands)

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

    2018-01-01

    textabstractHuman respiratory syncytial virus (HRSV) causes substantial morbidity and mortality in vulnerable patients, such as the very young, the elderly, and immunocompromised individuals of any age. Nosocomial transmission of HRSV remains a serious challenge in hospital settings, with

  12. 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.

  13. 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...

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

    Science.gov (United States)

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

    1997-03-01

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

  15. 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

    2018-05-01

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

  16. Respiratory Syncytial Virus (RSV)

    Centers for Disease Control (CDC) Podcasts

    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.

  17. 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.

  18. 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...

  19. 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.

  20. Computational Breakthrough of Natural Lead Hits from the Genus of Arisaema against 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.

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  3. 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...

  4. 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

    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.......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....... 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...

  5. A Two-Dimensional Human Minilung System (Model for Respiratory Syncytial Virus Infections

    Directory of Open Access Journals (Sweden)

    Esmeralda Magro-Lopez

    2017-12-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of serious pediatric respiratory diseases that lacks effective vaccine or specific therapeutics. Although our understanding about HRSV biology has dramatically increased during the last decades, the need for adequate models of HRSV infection is compelling. We have generated a two-dimensional minilung from human embryonic stem cells (hESCs. The differentiation protocol yielded at least six types of lung and airway cells, although it is biased toward the generation of distal cells. We show evidence of HRSV replication in lung cells, and the induction of innate and proinflammatory responses, thus supporting its use as a model for the study of HRSV–host interactions.

  6. The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Silke M Currie

    Full Text Available Respiratory syncytial virus is a leading cause of lower respiratory tract illness among infants, the elderly and immunocompromised individuals. Currently, there is no effective vaccine or disease modifying treatment available and novel interventions are urgently required. Cathelicidins are cationic host defence peptides expressed in the inflamed lung, with key roles in innate host defence against infection. We demonstrate that the human cathelicidin LL-37 has effective antiviral activity against RSV in vitro, retained by a truncated central peptide fragment. LL-37 prevented virus-induced cell death in epithelial cultures, significantly inhibited the production of new infectious particles and diminished the spread of infection, with antiviral effects directed both against the viral particles and the epithelial cells. LL-37 may represent an important targetable component of innate host defence against RSV infection. Prophylactic modulation of LL-37 expression and/or use of synthetic analogues post-infection may represent future novel strategies against RSV infection.

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

    Science.gov (United States)

    Pickles, Raymond J

    2013-01-01

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

  8. 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

  9. 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

  10. An ultrastructural study of the interaction of human eosinophils with respiratory syncytial virus

    NARCIS (Netherlands)

    Kimpen, JLL; Garofalo, R; Welliver, RC; Fujihara, K; Ogra, PL

    It was shown previously that eosinophils are activated in vivo and in vitro by respiratory syncytial virus (RSV) (Garofalo et al., J Pediatr 1992: 120: 28-32; Kimpen et al., Pediatr Res 1992: 32: 160-4). For study of the interaction of eosinophils and RSV on the ultrastructural level, normodense

  11. 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

  12. Functional Impairment of Mononuclear Phagocyte System by the Human Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Karen Bohmwald

    2017-11-01

    Full Text Available The mononuclear phagocyte system (MPS comprises of monocytes, macrophages (MΦ, and dendritic cells (DCs. MPS is part of the first line of immune defense against a wide range of pathogens, including viruses, such as the human respiratory syncytial virus (hRSV. The hRSV is an enveloped virus that belongs to the Pneumoviridae family, Orthopneumovirus genus. This virus is the main etiological agent causing severe acute lower respiratory tract infection, especially in infants, children and the elderly. Human RSV can cause bronchiolitis and pneumonia and it has also been implicated in the development of recurrent wheezing and asthma. Monocytes, MΦ, and DCs significantly contribute to acute inflammation during hRSV-induced bronchiolitis and asthma exacerbation. Furthermore, these cells seem to be an important component for the association between hRSV and reactive airway disease. After hRSV infection, the first cells encountered by the virus are respiratory epithelial cells, alveolar macrophages (AMs, DCs, and monocytes in the airways. Because AMs constitute the predominant cell population at the alveolar space in healthy subjects, these cells work as major innate sentinels for the recognition of pathogens. Although adaptive immunity is crucial for viral clearance, AMs are required for the early immune response against hRSV, promoting viral clearance and controlling immunopathology. Furthermore, exposure to hRSV may affect the phagocytic and microbicidal capacity of monocytes and MΦs against other infectious agents. Finally, different studies have addressed the roles of different DC subsets during infection by hRSV. In this review article, we discuss the role of the lung MPS during hRSV infection and their involvement in the development of bronchiolitis.

  13. Phosphorylation of human respiratory syncytial virus P protein at serine 54 regulates viral uncoating

    International Nuclear Information System (INIS)

    Asenjo, Ana; Gonzalez-Armas, Juan C.; Villanueva, Nieves

    2008-01-01

    The human respiratory syncytial virus (HRSV) structural P protein, phosphorylated at serine (S) and threonine (T) residues, is a co-factor of viral RNA polymerase. The phosphorylation of S54 is controlled by the coordinated action of two cellular enzymes: a lithium-sensitive kinase, probably glycogen synthetase kinase (GSK-3) β and protein phosphatase 2A (PP2A). Inhibition of lithium-sensitive kinase, soon after infection, blocks the viral growth cycle by inhibiting synthesis and/or accumulation of viral RNAs, proteins and extracellular particles. P protein phosphorylation at S54 is required to liberate viral ribonucleoproteins (RNPs) from M protein, during the uncoating process. Kinase inhibition, late in infection, produces a decrease in genomic RNA and infectious viral particles. LiCl, intranasally applied to mice infected with HRSV A2 strain, reduces the number of mice with virus in their lungs and the virus titre. Administration of LiCl to humans via aerosol should prevent HRSV infection, without secondary effects

  14. Transmission of Human Respiratory Syncytial Virus in the Immunocompromised Ferret Model

    Science.gov (United States)

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

    2018-01-01

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

  15. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

    International Nuclear Information System (INIS)

    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet; Quistgaard, Esben M.; Nordlund, Par; Thanabalu, Thirumaran; Torres, Jaume

    2015-01-01

    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

  16. 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.

  17. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Ascough, Stephanie; Paterson, Suzanna; Chiu, Christopher

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Stephanie Ascough

    2018-03-01

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

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

    African Journals Online (AJOL)

    Tharwat Ezzat Deraz

    2012-02-28

    Feb 28, 2012 ... Abstract Background: Respiratory syncytial virus (RSV) types A and B and influenza A and B cause about .... plied Science, Mannheim, Germany; Cat. ..... detection of human rhinoviruses, paramyxoviruses, corona viruses, and ...

  2. Elevated temperature triggers human respiratory syncytial virus F protein six-helix bundle formation

    International Nuclear Information System (INIS)

    Yunus, Abdul S.; Jackson, Trent P.; Crisafi, Katherine; Burimski, Irina; Kilgore, Nicole R.; Zoumplis, Dorian; Allaway, Graham P.; Wild, Carl T.; Salzwedel, Karl

    2010-01-01

    Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection in infants, immunocompromised patients, and the elderly. The RSV fusion (F) protein mediates fusion of the viral envelope with the target cell membrane during virus entry and is a primary target for antiviral drug and vaccine development. The F protein contains two heptad repeat regions, HR1 and HR2. Peptides corresponding to these regions form a six-helix bundle structure that is thought to play a critical role in membrane fusion. However, characterization of six-helix bundle formation in native RSV F protein has been hindered by the fact that a trigger for F protein conformational change has yet to be identified. Here we demonstrate that RSV F protein on the surface of infected cells undergoes a conformational change following exposure to elevated temperature, resulting in the formation of the six-helix bundle structure. We first generated and characterized six-helix bundle-specific antibodies raised against recombinant peptides modeling the RSV F protein six-helix bundle structure. We then used these antibodies as probes to monitor RSV F protein six-helix bundle formation in response to a diverse array of potential triggers of conformational changes. We found that exposure of 'membrane-anchored' RSV F protein to elevated temperature (45-55 deg. C) was sufficient to trigger six-helix bundle formation. Antibody binding to the six-helix bundle conformation was detected by both flow cytometry and cell-surface immunoprecipitation of the RSV F protein. None of the other treatments, including interaction with a number of potential receptors, resulted in significant binding by six-helix bundle-specific antibodies. We conclude that native, untriggered RSV F protein exists in a metastable state that can be converted in vitro to the more stable, fusogenic six-helix bundle conformation by an increase in thermal energy. These findings help to better define the mechanism of

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

    Science.gov (United States)

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

    2012-01-01

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

  4. Learn about Respiratory Syncytial Virus (RSV)

    Science.gov (United States)

    ... the Planet and Lung Health by Reducing Air Pollution Blog: JUUL: A Wolf in Sheep's Clothing '; } else { ... while processing XML file."); } }); } } --> Blank Section Header Lung Disease Lookup RSV Learn About Respiratory Syncytial Virus (RSV) RSV Symptoms, Causes & Risk Factors ...

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

    Science.gov (United States)

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

    2017-09-02

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

  6. 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

    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...... 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......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...

  7. 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...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Koert J. Stittelaar

    2016-06-01

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

  10. Gold nanorod vaccine for respiratory syncytial virus

    International Nuclear Information System (INIS)

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

    2013-01-01

    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. (paper)

  11. Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

    Science.gov (United States)

    Leemans, A; De Schryver, M; Van der Gucht, W; Heykers, A; Pintelon, I; Hotard, A L; Moore, M L; Melero, J A; McLellan, J S; Graham, B S; Broadbent, L; Power, U F; Caljon, G; Cos, P; Maes, L; Delputte, P

    2017-07-15

    Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication. IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are

  12. 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.

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Viviane F Botosso

    2009-01-01

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

  16. Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection

    Directory of Open Access Journals (Sweden)

    Zhiwu Sun

    2015-02-01

    Full Text Available Respiratory syncytial virus (RSV is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP of RSV infection in children at high risk. We found that maleic anhydride (ML-modified human serum albumin (HSA, designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.

  17. Water extract of Pueraria lobata Ohwi has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

    Directory of Open Access Journals (Sweden)

    Tzeng-Jih Lin

    2013-12-01

    Full Text Available Human respiratory syncytial virus (HRSV infects all age groups and causes bronchiolitis, pneumonia, and acute respiratory distress syndrome with a significant mortality rate. To date, only ribavirin has been used to manage HRSV infection. However, ribavirin is expensive with an only modest effect. Furthermore, ribavirin has several side effects, which means it has limited clinical benefit. Pueraria lobata Ohwi (P. lobata is a common ingredient of Ge-Gen-Tang (Kakkon-to and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to, which are prescriptions of Chinese traditional medicine proven to have antiviral activity against HRSV. Therefore, it was hypothesized that P. lobata might be effective against HRSV. To find a cost-effective therapeutic modality, both human upper (HEp-2 and lower (A549 respiratory tract cell lines were used to test the hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results showed that the water extract of P. lobata was effective (p < 0.0001 against HRSV-induced plaque formation. P. lobata was more effective when given prior to viral inoculation (p < 0.0001 by inhibiting viral attachment (p < 0.0001 and penetration (p < 0.0001. However, supplementation with P. lobata could not stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has antiviral activity against HRSV-induced plaque formation in airway mucosa mainly by inhibiting viral attachment and internalization. Further identification of effective constituents could contribute to the prevention of HRSV infection.

  18. 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

    Introduction The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear. Materials and Methods We conducted a prospective, household-based cohort study of children aged factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01). Conclusion In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses among young children from developing countries. PMID:26107630

  19. Structural and Nonstructural Viral Proteins Are Targets of T-Helper Immune Response against Human Respiratory Syncytial Virus.

    Science.gov (United States)

    Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Mir, Carmen; Gebe, John A; Admon, Arie; López, Daniel

    2016-06-01

    Proper antiviral humoral and cellular immune responses require previous recognition of viral antigenic peptides that are bound to HLA class II molecules, which are exposed on the surface of antigen-presenting cells. The helper immune response is critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, a virus with severe health risk in infected pediatric, immunocompromised, and elderly populations. In this study, using a mass spectrometry analysis of complex HLA class II-bound peptide pools that were isolated from large amounts of HRSV-infected cells, 19 naturally processed HLA-DR ligands, most of them included in a complex nested set of peptides, were identified. Both the immunoprevalence and the immunodominance of the HLA class II response to HRSV were focused on one nonstructural (NS1) and two structural (matrix and mainly fusion) proteins of the infective virus. These findings have clear implications for analysis of the helper immune response as well as for antiviral vaccine design. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Hilar enlargement in respiratory syncytial virus pneumonia

    International Nuclear Information System (INIS)

    Odita, J.C.; Aghahowa, J.E.; Nwankwo, M.

    1989-01-01

    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.)

  1. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  2. 21 CFR 866.3480 - Respiratory syncytial virus serological reagents.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3480... respiratory syncytial viruses from clinical specimens or from tissue culture isolates derived from clinical...

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

    Science.gov (United States)

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

    2016-06-27

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

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

    African Journals Online (AJOL)

    disease and poor outcomes when exposed to the influenza virus. Studies of CTL responses ... (IL)8 and IL2) and human neutrophil elastase play a significant ~ role in the ..... Prophylaxis against respiratory syncytial virus in premature infants.

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

    Science.gov (United States)

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

    2017-04-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589-597, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

  7. Proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology.

    Science.gov (United States)

    Munday, Diane C; Howell, Gareth; Barr, John N; Hiscox, Julian A

    2015-03-01

    The aim of this study was to quantitatively characterise the mitochondrial proteome of airway epithelial cells infected with human respiratory syncytial virus (HRSV), a major cause of paediatric illness. Quantitative proteomics, underpinned by stable isotope labelling with amino acids in cell culture, coupled to LC-MS/MS, was applied to mitochondrial fractions prepared from HRSV-infected and mock-infected cells 12 and 24 h post-infection. Datasets were analysed using ingenuity pathway analysis, and the results were validated and characterised using bioimaging, targeted inhibition and gene depletion. The data quantitatively indicated that antiviral signalling proteins converged on mitochondria during HRSV infection. The mitochondrial receptor protein Tom70 was found to act in an antiviral manner, while its chaperone, Hsp90, was confirmed to be a positive viral factor. Proteins associated with different organelles were also co-enriched in the mitochondrial fractions from HRSV-infected cells, suggesting that alterations in organelle dynamics and membrane associations occur during virus infection. Protein and pathway-specific alterations occur to the mitochondrial proteome in a spatial and temporal manner during HRSV infection, suggesting that this organelle may have altered functions. These could be targeted as part of potential therapeutic strategies to disrupt virus biology. © 2014 Royal Pharmaceutical Society.

  8. Strategies for preventing respiratory syncytial virus.

    Science.gov (United States)

    Forbes, Michael

    2008-12-01

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

  9. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

    International Nuclear Information System (INIS)

    Palomo, Concepción; Mas, Vicente; Vázquez, Mónica; Cano, Olga; Luque, Daniel; Terrón, María C.; Calder, Lesley J.; Melero, José A.

    2014-01-01

    Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV F occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV F , we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to explore the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV F at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy

  10. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    International Nuclear Information System (INIS)

    Jumat, Muhammad Raihan; Yan, Yan; Ravi, Laxmi Iyer; Wong, Puisan; Huong, Tra Nguyen; Li, Chunwei; Tan, Boon Huan; Wang, De Yun; Sugrue, Richard J.

    2015-01-01

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function

  11. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    Energy Technology Data Exchange (ETDEWEB)

    Jumat, Muhammad Raihan [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Yan, Yan [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Ravi, Laxmi Iyer [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Wong, Puisan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Huong, Tra Nguyen [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Li, Chunwei [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Tan, Boon Huan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Wang, De Yun [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Sugrue, Richard J., E-mail: rjsugrue@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)

    2015-10-15

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function.

  12. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, Concepción; Mas, Vicente; Vázquez, Mónica; Cano, Olga [Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid (Spain); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain); Luque, Daniel; Terrón, María C. [Unidad de Microscopía Electrónica y Confocal, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain); Calder, Lesley J. [National Institute for Medical Research, MRC, Mill Hill, London NW7 1AA (United Kingdom); Melero, José A., E-mail: jmelero@isciii.es [Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid (Spain); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain)

    2014-07-15

    Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV{sub F} occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV{sub F}, we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to explore the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV{sub F} at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy.

  13. 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.

  14. 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

  15. 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

  16. Whole genome sequencing and evolutionary analysis of human respiratory syncytial virus A and B from Milwaukee, WI 1998-2010.

    Directory of Open Access Journals (Sweden)

    Cecilia Rebuffo-Scheer

    Full Text Available BACKGROUND: Respiratory Syncytial Virus (RSV is the leading cause of lower respiratory-tract infections in infants and young children worldwide. Despite this, only six complete genome sequences of original strains have been previously published, the most recent of which dates back 35 and 26 years for RSV group A and group B respectively. METHODOLOGY/PRINCIPAL FINDINGS: We present a semi-automated sequencing method allowing for the sequencing of four RSV whole genomes simultaneously. We were able to sequence the complete coding sequences of 13 RSV A and 4 RSV B strains from Milwaukee collected from 1998-2010. Another 12 RSV A and 5 RSV B strains sequenced in this study cover the majority of the genome. All RSV A and RSV B sequences were analyzed by neighbor-joining, maximum parsimony and Bayesian phylogeny methods. Genetic diversity was high among RSV A viruses in Milwaukee including the circulation of multiple genotypes (GA1, GA2, GA5, GA7 with GA2 persisting throughout the 13 years of the study. However, RSV B genomes showed little variation with all belonging to the BA genotype. For RSV A, the same evolutionary patterns and clades were seen consistently across the whole genome including all intergenic, coding, and non-coding regions sequences. CONCLUSIONS/SIGNIFICANCE: The sequencing strategy presented in this work allows for RSV A and B genomes to be sequenced simultaneously in two working days and with a low cost. We have significantly increased the amount of genomic data that is available for both RSV A and B, providing the basic molecular characteristics of RSV strains circulating in Milwaukee over the last 13 years. This information can be used for comparative analysis with strains circulating in other communities around the world which should also help with the development of new strategies for control of RSV, specifically vaccine development and improvement of RSV diagnostics.

  17. Epidemiology and Molecular Characterization of Human Respiratory Syncytial Virus in Senegal after Four Consecutive Years of Surveillance, 2012–2015

    Science.gov (United States)

    Cisse, El Hadj Abdel Kader; Kiori, Davy E.; Sarr, Fatoumata Diene; Sy, Sara; Goudiaby, Debora; Richard, Vincent; Niang, Mbayame Ndiaye

    2016-01-01

    Background The burden of respiratory syncytial virus (RSV) infection remains poorly defined in Africa. To address this, we carried out a descriptive and retrospective pilot study, with a focus on the epidemiology of RSV in Senegal after 4 years of surveillance. Methodology and Results From January 2012 to October 2015 swabs were collected from consenting ILI outpatients. Viral detection was performed using RV16 kit enabling direct subtyping of RSV-A and B. For the molecular characterization of HRSV, the second hypervariable region of the Glycoprotein (G) gene was targeted for sequencing. We enrolled 5338 patients with 2803 children younger than five years of age (52.5%). 610 (11.4%) were positive for RSV infection: 276 (45.2%) were group A infections, 334 (54.8%) were group B infections and 21 (3.4%) were A/B co-infections. RSV detection rate is significantly higher (P Senegal clustered with strains that were previously assigned NA1 and novel ON1 genotype sequences. RSV-B sequences from Senegal clustered with the BA9 genotype. At the amino acid level, RSV-A strains from Senegal show proximity with the genotype ON1 characterized by a 72 nt insertion in G, resulting in 24 extra amino acids of which 23 are duplications of aa 261–283. Conclusion Globally our results show a clear circulation pattern of RSV in the second half of each year, between June and September and possibly extending into November, with children under 5 being more susceptible. Molecular studies identified the novel strains ON1 and BA9 as the major genotypes circulating in Senegal between 2012 and 2015. PMID:27315120

  18. Epidemiology and Molecular Characterization of Human Respiratory Syncytial Virus in Senegal after Four Consecutive Years of Surveillance, 2012-2015.

    Science.gov (United States)

    Fall, Amary; Dia, Ndongo; Cisse, El Hadj Abdel Kader; Kiori, Davy E; Sarr, Fatoumata Diene; Sy, Sara; Goudiaby, Debora; Richard, Vincent; Niang, Mbayame Ndiaye

    2016-01-01

    The burden of respiratory syncytial virus (RSV) infection remains poorly defined in Africa. To address this, we carried out a descriptive and retrospective pilot study, with a focus on the epidemiology of RSV in Senegal after 4 years of surveillance. From January 2012 to October 2015 swabs were collected from consenting ILI outpatients. Viral detection was performed using RV16 kit enabling direct subtyping of RSV-A and B. For the molecular characterization of HRSV, the second hypervariable region of the Glycoprotein (G) gene was targeted for sequencing. We enrolled 5338 patients with 2803 children younger than five years of age (52.5%). 610 (11.4%) were positive for RSV infection: 276 (45.2%) were group A infections, 334 (54.8%) were group B infections and 21 (3.4%) were A/B co-infections. RSV detection rate is significantly higher (P Senegal clustered with strains that were previously assigned NA1 and novel ON1 genotype sequences. RSV-B sequences from Senegal clustered with the BA9 genotype. At the amino acid level, RSV-A strains from Senegal show proximity with the genotype ON1 characterized by a 72 nt insertion in G, resulting in 24 extra amino acids of which 23 are duplications of aa 261-283. Globally our results show a clear circulation pattern of RSV in the second half of each year, between June and September and possibly extending into November, with children under 5 being more susceptible. Molecular studies identified the novel strains ON1 and BA9 as the major genotypes circulating in Senegal between 2012 and 2015.

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

    Science.gov (United States)

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

  20. Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure

    Directory of Open Access Journals (Sweden)

    Claudia Trigo Pedroso Moraes

    2015-02-01

    Full Text Available Human respiratory syncytial virus (HRSV is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

  1. Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure.

    Science.gov (United States)

    Moraes, Claudia Trigo Pedroso; Oliveira, Danielle Bruna Leal; Campos, Angelica Cristine Almeida; Bosso, Patricia Alves; Lima, Hildener Nogueira; Stewien, Klaus Eberhard; Gilio, Alfredo Elias; Vieira, Sandra Elisabete; Botosso, Viviane Fongaro; Durigon, Edison Luiz

    2015-02-01

    Human respiratory syncytial virus (HRSV) is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn) in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro) in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

  2. 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 viru...

  3. Respiratory syncytial virus infection induces higher Toll-like receptor-3 expression and TNF-α production than human metapneumovirus infection.

    Directory of Open Access Journals (Sweden)

    Ying Dou

    Full Text Available Respiratory syncytial virus (RSV and human metapneumovirus (hMPV are common causes of respiratory infections in children. Diseases caused by hMPV are generally considered to be less severe than those caused by RSV; the underlying mechanisms, however, remain unknown. In the present study, the expressions of TLRs in airway epithelial cells and lungs of BALB/c mice infected by hMPV or RSV were measured in an attempt to explore the differences in the airway inflammation caused by the two viruses. Our results demonstrate that both hMPV and RSV infection upregulated the expressions of TLRs and inflammatory cytokines. Specifically, the TLR3 expression was revealed to be elevated in vitro and in mouse lungs. IFN-α produced by A549 cells after RSV or hMPV infection remained undistinguishable, whereas production of TNF-α was significantly higher after RSV infection than hMPV infection either in the presence or absence of Poly I:C. This study provides a clue that more severe clinical syndrome of RSV infection may be due to the greater magnitude of induction of airway inflammation by RSV involving TLR3 activation and production of TNF-α.

  4. Genetic and antigenic analysis of the G attachment protein of bovine respiratory syncytial virus strains

    DEFF Research Database (Denmark)

    Elvander, M.; Vilcek, S.; Baule, C.

    1998-01-01

    Antigenic and genetic studies of bovine respiratory syncytial virus (BRSV) were made on isolates obtained from three continents over 27 years. Antigenic variation between eight isolates was initially determined using protein G-specific monoclonal antibodies. Four distinct reaction patterns were...... of a 731 nucleotide fragment in the G protein gene. Nine of the BRSV strains were analysed by direct sequencing of RT-PCR amplicons whereas sequences of 18 BRSV and three human respiratory syncytial virus (HRSV) strains were obtained from GenBank. The analysis revealed similarities of 88-100% among BRSV...

  5. Burden of Respiratory Syncytial Virus Infection in South African Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Pregnant and Postpartum Women: A Longitudinal Cohort Study.

    Science.gov (United States)

    Madhi, Shabir A; Cutland, Clare L; Downs, Sarah; Jones, Stephanie; van Niekerk, Nadia; Simoes, Eric A F; Nunes, Marta C

    2018-05-17

    Limited data exist on the burden of respiratory syncytial virus (RSV) illness among pregnant women, to determine their potential benefit from RSV vaccination. We evaluated the incidence of RSV illness from midpregnancy until 24 weeks postpartum in human immunodeficiency virus (HIV)-uninfected and HIV-infected women and their infants. Mother-infant dyads were enrolled in maternal influenza vaccine efficacy trials. These included 1060 and 1056 HIV-uninfected pregnant women in 2011 and 2012, respectively, 194 HIV-infected pregnant women in 2011, and their infants. Upper respiratory tract samples obtained at illness visits were tested for RSV. The incidence (per 1000 person-months) of RSV illness (n = 43 overall) among HIV-uninfected women was lower in 2011 (1.2; 95% confidence interval [CI], .6-2.2) than in 2012 (4.0; 95% CI, 2.8-5.6). The incidence of RSV illness (n = 5) in HIV-infected women was 3.4 (95% CI, 1.4-8.1). Maternal RSV infection was associated with respiratory symptoms including cough (72.1%), rhinorrhea (39.5%), sore throat (37.2%), and headache (42%), but fever was absent. RSV infection during pregnancy was not associated with adverse pregnancy outcomes. Postpartum, RSV infection in mothers (n = 27) was associated with concurrent infection among 51.9% of their infants and, conversely, 29.8% of mothers investigated within 7 days of their infants having an RSV illness also tested positive for RSV. RSV infection is associated with respiratory illness during pregnancy and postpartum. Vaccination of pregnant women against RSV could benefit the mother, albeit primarily against nonfebrile illness, and her infant. NCT01306669 and NCT01306682.

  6. 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-neutralizing antib......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......-neutralizing antibody level plays a role in the RSV seasonal pattern....

  7. A prime-boost vaccination strategy using attenuated Salmonella typhimurium and a replication-deficient recombinant adenovirus vector elicits protective immunity against human respiratory syncytial virus.

    Science.gov (United States)

    Fu, Yuan-Hui; He, Jin-Sheng; Wang, Xiao-Bo; Zheng, Xian-Xian; Wu, Qiang; Xie, Can; Zhang, Mei; Wei, Wei; Tang, Qian; Song, Jing-Dong; Qu, Jian-Guo; Hong, Tao

    2010-04-23

    Human respiratory syncytial virus (RSV), for which no clinically approved vaccine is available yet, is globally a serious pediatric pathogen of the lower respiratory tract. Several approaches have been used to develop vaccines against RSV, but none of these have been approved for use in humans. An efficient vaccine-enhancing strategy for RSV is still urgently needed. We found previously that oral SL7207/pcDNA3.1/F and intranasal FGAd/F were able to induce an effective protective immune response against RSV. The heterologous prime-boost immunization regime has been reported recently to be an efficient vaccine-enhancing strategy. Therefore, we investigated the ability of an oral SL7207/pcDNA3.1/F prime and intranasal (i.n.) FGAd/F boost regimen to generate immune responses to RSV. The SL7207/pcDNA3.1/F prime-FGAd/F boost regimen generated stronger RSV-specific humoral and mucosal immune responses in BALB/c mice than the oral SL7207/pcDNA3.1/F regimen alone, and stronger specific cellular immune responses than the i.n. FGAd/F regimen alone. Histopathological analysis showed an increased efficacy against RSV challenge by the heterologous prime-boost regimen. These results suggest that such a heterologous prime-boost strategy can enhance the efficacy of either the SL7207 or the FGAd vector regimen in generating immune responses in BALB/c mice. 2010 Elsevier Inc. All rights reserved.

  8. Recombinant Human Respiratory Syncytial Virus (RSV) Monoclonal Antibody Fab is Effective Therapeutically when Introduced Directly into the Lungs of RSV-Infected Mice

    Science.gov (United States)

    Crowe, James E., Jr.; Murphy, Brian R.; Chanock, Robert M.; Williamson, R. Anthony; Barbas, Carlos F., III; Burton, Dennis R.

    1994-02-01

    Previously, recombinant human respiratory syncytial virus (RSV) monoclonal antibody Fabs were generated by antigen selection from random combinatorial libraries displayed at the tip of filamentous phage. Two such Fabs, which exhibited high binding affinity for RSV F glycoprotein (a major protective antigen), were evaluated for therapeutic efficacy in infected mice just before or at the time of peak virus replication in the lungs. Fab 19, which neutralized RSV infectivity with high efficiency in tissue culture, was effective therapeutically when delivered directly into the lungs by intranasal instillation under anesthesia. In contrast, RSV Fab 126, which failed to neutralize virus in cell culture, did not exhibit a therapeutic effect under these conditions. The amount of Fab 19 required to effect a 5000- to 12,000-fold reduction in titer of RSV in the lungs within 24 hr was rather small. In four separate experiments, a single instillation of 12.9-50 μg of RSV Fab 19 was sufficient to achieve such a reduction in pulmonary virus in a 25g mouse. The use of Fabs instead of the whole immunoglobulin molecules from which they are derived reduced the protein content of a therapeutic dose. This is important because the protein load that can be delivered effectively into the lungs is limited. The therapeutic effect of a single treatment with Fab 19 was not sustained, so that a rebound in pulmonary virus titer occurred on the 2nd day after treatment. This rebound in pulmonary RSV titer could be prevented by treating infected mice with a single dose of Fab 19 daily for 3 days. These observations suggest that human monoclonal Fabs grown in Escherichia coli may prove useful in the treatment of serious RSV disease as well as diseases caused by other viruses where replication in vivo is limited primarily to the lumenal lining of the respiratory tract.

  9. A single intranasal administration of virus-like particle vaccine induces an efficient protection for mice against human respiratory syncytial virus.

    Science.gov (United States)

    Jiao, Yue-Ying; Fu, Yuan-Hui; Yan, Yi-Fei; Hua, Ying; Ma, Yao; Zhang, Xiu-Juan; Song, Jing-Dong; Peng, Xiang-Lei; Huang, Jiaqiang; Hong, Tao; He, Jin-Sheng

    2017-08-01

    Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully. The resulting VLPs showed similar immunoreactivity and function to RSV virion in vitro. Moreover, Th1 polarized response, and effective mucosal virus-neutralizing antibody and CD8 + T-cell responses were induced by a single intranasal (i.n.) administration of RSV VLPs rather than intramuscular (i.m.) inoculation, although the comparable RSV F-specific serum IgG and long-lasting RSV-specific neutralizing antibody were detected in the mice immunized by both routes. Upon RSV challenge, VLP-immunized mice showed increased viral clearance but decreased signs of enhanced lung pathology and fewer eosinophils compared to mice immunized with formalin-inactivated RSV (FI-RSV). In addition, a single i.n. RSV VLP vaccine has the capability to induce RSV-specific long-lasting neutralizing antibody responses observable up to 15 months. Our results demonstrate that the long-term and memory immune responses in mice against RSV were induced by a single i.n. administration of RSV VLP vaccine, suggesting a successful approach of RSV VLPs as an effective and safe mucosal vaccine against RSV infection, and an applicable and qualified platform of FGAd-infected Vero cells for VLP production. Copyright © 2017. Published by Elsevier B.V.

  10. Multiple Functional Domains and Complexes of the Two Nonstructural Proteins of Human Respiratory Syncytial Virus Contribute to Interferon Suppression and Cellular Location▿

    Science.gov (United States)

    Swedan, Samer; Andrews, Joel; Majumdar, Tanmay; Musiyenko, Alla; Barik, Sailen

    2011-01-01

    Human respiratory syncytial virus (RSV), a major cause of severe respiratory diseases, efficiently suppresses cellular innate immunity, represented by type I interferon (IFN), using its two unique nonstructural proteins, NS1 and NS2. In a search for their mechanism, NS1 was previously shown to decrease levels of TRAF3 and IKKε, whereas NS2 interacted with RIG-I and decreased TRAF3 and STAT2. Here, we report on the interaction, cellular localization, and functional domains of these two proteins. We show that recombinant NS1 and NS2, expressed in lung epithelial A549 cells, can form homo- as well as heteromers. Interestingly, when expressed alone, substantial amounts of NS1 and NS2 localized to the nuclei and to the mitochondria, respectively. However, when coexpressed with NS2, as in RSV infection, NS1 could be detected in the mitochondria as well, suggesting that the NS1-NS2 heteromer localizes to the mitochondria. The C-terminal tetrapeptide sequence, DLNP, common to both NS1 and NS2, was required for some functions, but not all, whereas only the NS1 N-terminal region was important for IKKε reduction. Finally, NS1 and NS2 both interacted specifically with host microtubule-associated protein 1B (MAP1B). The contribution of MAP1B in NS1 function was not tested, but in NS2 it was essential for STAT2 destruction, suggesting a role of the novel DLNP motif in protein-protein interaction and IFN suppression. PMID:21795342

  11. Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication.

    Directory of Open Access Journals (Sweden)

    Alireza Eshaghi

    Full Text Available Human respiratory syncytial virus (HRSV is the main cause of acute lower respiratory infections in children under 2 years of age and causes repeated infections throughout life. We investigated the genetic variability of RSV-A circulating in Ontario during 2010-2011 winter season by sequencing and phylogenetic analysis of the G glycoprotein gene.Among the 201 consecutive RSV isolates studied, RSV-A (55.7% was more commonly observed than RSV-B (42.3%. 59.8% and 90.1% of RSV-A infections were among children ≤12 months and ≤5 years old, respectively. On phylogenetic analysis of the second hypervariable region of the 112 RSV-A strains, 110 (98.2% clustered within or adjacent to the NA1 genotype; two isolates were GA5 genotype. Eleven (10% NA1-related isolates clustered together phylogenetically as a novel RSV-A genotype, named ON1, containing a 72 nucleotide duplication in the C-terminal region of the attachment (G glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and includes a23 amino acid duplication. Using RNA secondary structural software, a possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G gene duplication results in a repeat of 7 potential O-glycosylation sites including three O-linked sugar acceptors at residues 270, 275, and 283. Using Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively selected sites were observed among Ontario NA1 isolates; six were found to be codons which reverted to the previous state observed in the prototype RSV-A2 strain. The tendency of codon regression in the G-ectodomain may infer a decreased avidity of antibody to the current circulating strains. Further work is needed to document and further understand the emergence, virulence, pathogenicity and transmissibility of this novel RSV-A genotype with a72 nucleotide G gene duplication.

  12. Management of the infant with respiratory syncytial virus.

    Science.gov (United States)

    Corey, M A; Clore, E R

    1991-04-01

    This article examines updated clinical information concerning respiratory syncytial virus (RSV) infection including epidemiology, pathology, clinical manifestations, diagnosis, treatment, nosocomial infection, and prognosis. Also presented is current information on ribavirin therapy, its side effects, and precautions. Research related to the most effective isolation methodology is discussed, as well as nursing diagnoses based on Gordon's Functional Health Patterns and interventions for the infant hospitalized with RSV bronchiolitis and/or pneumonia.

  13. Phosphorylation of the human respiratory syncytial virus P protein mediates M2-2 regulation of viral RNA synthesis, a process that involves two P proteins.

    Science.gov (United States)

    Asenjo, Ana; Villanueva, Nieves

    2016-01-04

    The M2-2 protein regulates the balance between human respiratory syncytial virus (HRSV) transcription and replication. Here it is shown that M2-2 mediated transcriptional inhibition is managed through P protein phosphorylation. Transcription inhibition by M2-2 of the HRSV based minigenome pRSVluc, required P protein phosphorylation at serines (S) in positions 116, 117, 119 and increased inhibition is observed if S232 or S237 is also phosphorylated. Phosphorylation of these residues is required for viral particle egression from infected cells. Viral RNA synthesis complementation assays between P protein variants, suggest that two types of P proteins participate in the process as components of RNA dependent RNA polymerase (RdRp). Type I is only functional when, as a homotetramer, it is bound to N and L proteins through residues 203-241. Type II is functionally independent of these interactions and binds to N protein at a region outside residues 232-241. P protein type I phosphorylation at S116, S117 and S119, did not affect the activity of RdRp but this phosphorylation in type II avoids its interaction with N protein and impairs RdRp functionality for transcription and replication. Structural changes in the RdRp, mediated by phosphorylation turnover at the indicated residues, in the two types of P proteins, may result in a fine adjustment, late in the infectious cycle, of transcription, replication and progression in the morphogenetic process that ends in egression of the viral particles from infected cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Humane metapneumovirus (HMPV) associated pulmonary infections in immunocompromised adults—Initial CT findings, disease course and comparison to respiratory-syncytial-virus (RSV) induced pulmonary infections

    International Nuclear Information System (INIS)

    Syha, R.; Beck, R.; Hetzel, J.; Ketelsen, D.; Grosse, U.; Springer, F.; Horger, M.

    2012-01-01

    Aim: To describe computed tomography (CT)-imaging findings in human metapneumovirus (HMPV)-related pulmonary infection as well as their temporal course and to analyze resemblances/differences to pulmonary infection induced by the closely related respiratory-syncytial-virus (RSV) in immunocompromised patients. Materials and methods: Chest-CT-scans of 10 HMPV PCR-positive patients experiencing pulmonary symptoms were evaluated retrospectively with respect to imaging findings and their distribution and results were then compared with data acquired in 13 patients with RSV pulmonary infection. Subsequently, we analyzed the course of chest-findings in HMPV patients. Results: In HMPV, 8/10 patients showed asymmetric pulmonary findings, whereas 13/13 patients with RSV-pneumonia presented more symmetrical bilateral pulmonary infiltrates. Image analysis yielded in HMPV patients following results: ground-glass-opacity (GGO) (n = 6), parenchymal airspace consolidations (n = 5), ill-defined nodular-like centrilobular opacities (n = 9), bronchial wall thickening (n = 8). In comparison, results in RSV patients were: GGO (n = 10), parenchymal airspace consolidations (n = 9), ill-defined nodular-like centrilobular opacities (n = 10), bronchial wall thickening (n = 4). In the course of the disease, signs of acute HMPV interstitial pneumonia regressed transforming temporarily in part into findings compatible with bronchitis/bronchiolitis. Conclusions: Early chest-CT findings in patients with HMPV-related pulmonary symptoms are compatible with asymmetric acute interstitial pneumonia accompanied by signs of bronchitis; the former transforming with time into bronchitis and bronchiolitis before they resolve. On the contrary, RSV-induced pulmonary infection exhibits mainly symmetric acute interstitial pneumonia.

  15. Humane metapneumovirus (HMPV) associated pulmonary infections in immunocompromised adults—Initial CT findings, disease course and comparison to respiratory-syncytial-virus (RSV) induced pulmonary infections

    Energy Technology Data Exchange (ETDEWEB)

    Syha, R., E-mail: roland.syha@med.uni-tuebingen.de [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen (Germany); Beck, R. [Institute of Medical Virology, Eberhard-Karls-University, Elfriede-Authorn-Str. 6, 72076 Tübingen (Germany); Hetzel, J. [Department of Medical Oncology and Hematology, Eberhard-Karls-University, Otfried-Müller-Str. 10, 72070 Tübingen (Germany); Ketelsen, D.; Grosse, U.; Springer, F.; Horger, M. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen (Germany)

    2012-12-15

    Aim: To describe computed tomography (CT)-imaging findings in human metapneumovirus (HMPV)-related pulmonary infection as well as their temporal course and to analyze resemblances/differences to pulmonary infection induced by the closely related respiratory-syncytial-virus (RSV) in immunocompromised patients. Materials and methods: Chest-CT-scans of 10 HMPV PCR-positive patients experiencing pulmonary symptoms were evaluated retrospectively with respect to imaging findings and their distribution and results were then compared with data acquired in 13 patients with RSV pulmonary infection. Subsequently, we analyzed the course of chest-findings in HMPV patients. Results: In HMPV, 8/10 patients showed asymmetric pulmonary findings, whereas 13/13 patients with RSV-pneumonia presented more symmetrical bilateral pulmonary infiltrates. Image analysis yielded in HMPV patients following results: ground-glass-opacity (GGO) (n = 6), parenchymal airspace consolidations (n = 5), ill-defined nodular-like centrilobular opacities (n = 9), bronchial wall thickening (n = 8). In comparison, results in RSV patients were: GGO (n = 10), parenchymal airspace consolidations (n = 9), ill-defined nodular-like centrilobular opacities (n = 10), bronchial wall thickening (n = 4). In the course of the disease, signs of acute HMPV interstitial pneumonia regressed transforming temporarily in part into findings compatible with bronchitis/bronchiolitis. Conclusions: Early chest-CT findings in patients with HMPV-related pulmonary symptoms are compatible with asymmetric acute interstitial pneumonia accompanied by signs of bronchitis; the former transforming with time into bronchitis and bronchiolitis before they resolve. On the contrary, RSV-induced pulmonary infection exhibits mainly symmetric acute interstitial pneumonia.

  16. 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

    (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...... of respiratory syncytial virus infection is determined partly by genetic factors. This result should stimulate the search for genetic markers of disease severity.......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...

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

    NARCIS (Netherlands)

    Bont, L.; Steijn, M.; van Aalderen, W. M. C.; Brus, F.; Th Draaisma, J. M.; van Diemen-Steenvoorde, R. A. A. M.; Pekelharing-Berghuis, M.; Kimpen, J. L. L.

    2004-01-01

    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

  18. 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

  19. 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

  20. A role for airway remodeling during respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Dimina Dawn M

    2005-10-01

    Full Text Available Abstract Background Severe respiratory syncytial virus infection (RSV during infancy has been shown to be a major risk factor for the development of subsequent wheeze. However, the reasons for this link remain unclear. The objective of this research was to determine the consequences of early exposure to RSV and allergen in the development of subsequent airway hyperreactivity (AHR using a developmental time point in the mouse that parallels that of the human neonate. Methods Weanling mice were sensitized and challenged with ovalbumin (Ova and/or infected with RSV. Eight days after the last allergen challenge, various pathophysiological endpoints were examined. Results AHR in response to methacholine was enhanced only in weanling mice exposed to Ova and subsequently infected with RSV. The increase in AHR appeared to be unrelated to pulmonary RSV titer. Total bronchoalveolar lavage cellularity in these mice increased approximately two-fold relative to Ova alone and was attributable to increases in eosinophil and lymphocyte numbers. Enhanced pulmonary pathologies including persistent mucus production and subepithelial fibrosis were observed. Interestingly, these data correlated with transient increases in TNF-α, IFN-γ, IL-5, and IL-2. Conclusion The observed changes in pulmonary structure may provide an explanation for epidemiological data suggesting that early exposure to allergens and RSV have long-term physiological consequences. Furthermore, the data presented here highlight the importance of preventative strategies against RSV infection of atopic individuals during neonatal development.

  1. Diversity and Adaptation of Human Respiratory Syncytial Virus Genotypes Circulating in Two Distinct Communities: Public Hospital and Day Care Center

    Directory of Open Access Journals (Sweden)

    Gustavo Rocha Garcia

    2012-10-01

    Full Text Available HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in São José do Rio Preto – SP, Brazil. We obtained partial sequences from G gene that were used on phylogenetic and selection pressure analysis. HRSV accounted for 29% of respiratory infections in hospitalized children and 7.7% in day care center children. On phylogenetic analysis of 60 HRSV strains, 48 (80% clustered within or adjacent to the GA1 genotype; GA5, NA1, NA2, BA-IV and SAB1 were also observed. SJRP GA1 strains presented variations among deduced amino acids composition and lost the potential O-glycosilation site at amino acid position 295, nevertheless this resulted in an insertion of two potential O-glycosilation sites at positions 296 and 297. Furthermore, a potential O-glycosilation site insertion, at position 293, was only observed for hospital strains. Using SLAC and MEME methods, only amino acid 274 was identified to be under positive selection. This is the first report on HRSV circulation and genotypes classification derived from a day care center community in Brazil.

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

    International Nuclear Information System (INIS)

    Kim, Woo Sun; Kim, In One; Yeon, Kyung Mo; Jang, Seong Hee; Lee, Hoan Jong

    1992-01-01

    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

  3. Human respiratory syncytial virus: prevalence, viral co-infections and risk factors for lower respiratory tract infections in children under 5 years of age at a general hospital in the Democratic Republic of Congo.

    Science.gov (United States)

    Kabego, Landry; Balol'Ebwami, Serge; Kasengi, Joe Bwija; Miyanga, Serge; Bahati, Yvette Lufungulo; Kambale, Richard; de Beer, Corena

    2018-04-01

    This study aimed to determine the prevalence of human respiratory syncytial virus (HRSV) acute respiratory infection (ARI) in children under the age of 5 years at the Provincial General Hospital of Bukavu (PGHB), and to analyse factors associated with the risk of ARI being diagnosed as lower respiratory tract infection (LRTI). A total of 146 children under 5 years visiting the PGHB for ARI between August and December 2016 were recruited, and socio-demographic information, clinical data and nasopharyngeal swabs were collected. The samples were analysed by a multiplex reverse transcriptase polymerase chain reaction targeting 15 different viruses. Of 146 samples collected, 84 (57.5 %) displayed a positive result of at least one of the 15 viruses. The overall prevalence of HRSV was 21.2 %. HRSV A (30, 20.5 %) was the virus the most detected, followed by HRV (24, 16.4 %), PIV3 (20, 16.6) and ADV (7, 4.79 %). The other viruses were detected in three or fewer cases. There were only 11 (7.5 %) cases of co-infection. HRSV infection, malnutrition, younger age, rural settings, low income and mother illiteracy were associated with the risk of ARI being diagnosed as LRTI in bivariate analyses but, after adjusting for the confounding factors, only HRSV infection and younger age were independently associated with LRTI. The prevalence of HRSV is high among children visiting the PGHB for ARI. HRSV infection and lower age are independently associated with the risk of ARI being diagnosed as LRTI.

  4. 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...

  5. 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

  6. 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

  7. 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,

  8. Effect of respiratory syncytial virus (RSV) infection on the adherence of pathogenic bacteria to human epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Faden, H.; Hong, J.J.; Ogra, P.L.

    1986-03-01

    The effect of RSV infection on the adherence of Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and Staphylococcus aureus (SA) to human epithelial cells was determined. RSV-infected Hep-2 cell cultures at different stages of expression of surface viral antigens and bacteria labeled with /sup 3/H-thymidine were employed to examine the kinetics of bacterial adherence to virus-infected cells. RSV infection did not alter the magnitude of adherence of HI or SA to HEp-2 cells. However, adherence of SP to HEp-2 cells was significantly (P < 0.01) enhanced by prior RSV infection. The degree of adherence was directly related to the amount of viral antigen expressed on the cell surface. The adherence was temperature dependent, with maximal adherence observed at 37/sup 0/C. Heat-inactivation of SP did not alter adherence characteristics. These data suggest that RSV infection increases adherence of SP to the surface of epithelial cells in vitro. Since attachment of bacteria to mucosal surfaces is the first step in many infections, it is suggested that viral infections of epithelial cells render them more susceptible to bacterial adherence. Thus, RSV infection in vivo may predispose children to SP infections, such as in otitis media, by increasing colonization with SP.

  9. Effect of respiratory syncytial virus (RSV) infection on the adherence of pathogenic bacteria to human epithelial cells

    International Nuclear Information System (INIS)

    Faden, H.; Hong, J.J.; Ogra, P.L.

    1986-01-01

    The effect of RSV infection on the adherence of Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and Staphylococcus aureus (SA) to human epithelial cells was determined. RSV-infected Hep-2 cell cultures at different stages of expression of surface viral antigens and bacteria labeled with 3 H-thymidine were employed to examine the kinetics of bacterial adherence to virus-infected cells. RSV infection did not alter the magnitude of adherence of HI or SA to HEp-2 cells. However, adherence of SP to HEp-2 cells was significantly (P 0 C. Heat-inactivation of SP did not alter adherence characteristics. These data suggest that RSV infection increases adherence of SP to the surface of epithelial cells in vitro. Since attachment of bacteria to mucosal surfaces is the first step in many infections, it is suggested that viral infections of epithelial cells render them more susceptible to bacterial adherence. Thus, RSV infection in vivo may predispose children to SP infections, such as in otitis media, by increasing colonization with SP

  10. 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.

  11. Bovine respiratory syncytial virus: first serological evidence in Uruguay.

    Science.gov (United States)

    Costa, M; García, L; Yunus, A S; Rockemann, D D; Samal, S K; Cristina, J

    2000-01-01

    Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in calves resulting in a substantial economic loss for the cattle industry worldwide. In order to determine the presence of BRSV in Uruguay, an immunoenzymatic test was set up, using a recombinant BRSV nucleocapsid (N) protein as the antigen. The N protein was produced in Sf9 insect cells by a recombinant baculovirus expressing the N protein. Serum samples collected from one hundred cattle from four different geographic regions of Uruguay were analyzed. Antibodies against the N protein of BRSV were detected in 95% of the serum samples analyzed. These results show for the first time the presence of BRSV antibodies and suggest a widespread BRSV infection in the cattle population of Uruguay.

  12. Respiratory syncytial virus mechanisms to interfere with type 1 interferons.

    Science.gov (United States)

    Barik, Sailen

    2013-01-01

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

  13. 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...

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

    Directory of Open Access Journals (Sweden)

    Flávio da Silva Mesquita

    2017-05-01

    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.

  15. 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

  16. Respiratory syncytial virus (RSV) pneumonia in a southern muriqui (Brachyteles arachnoides).

    Science.gov (United States)

    Santos, S V; Strefezzi, R F; Pissinatti, A; Takakura, C F H; Kanamura, C; Duarte, M I S; Catão-Dias, J L

    2012-12-01

    An adult male Brachyteles arachanoides, kept in captivity since 1990, was found dead without apparent clinical evidence. Necropsy report, histopathology, immunohistochemistry, and ultrastructural examination were conducted. Pulmonary syncytial cells were positive for respiratory syncytial virus (RSV), and ultrastructural examination revealed viral particles inside macrophages compatible with the Paramyxoviridae family. Muriquis are susceptible to RSV pneumonia followed by respiratory distress syndrome and death. © 2012 John Wiley & Sons A/S.

  17. Neonatal respiratory syncytial virus infection: role of transplacentally and breast milk-acquired antibodies.

    OpenAIRE

    Wong, D T; Ogra, P L

    1986-01-01

    The effect of transplacentally and breast milk-acquired antibodies on respiratory syncytial virus infection was studied in neonatal and 2-month-old cotton rats. Adult female rats infected intranasally with live virus regularly produced virus-specific antibodies in the serum, colostrum, and breast milk. By using foster feeding techniques, we showed that both transplacentally and breast milk-acquired antibodies were effective in reducing the replication of respiratory syncytial virus in the lun...

  18. Autonomic dysfunction with early respiratory syncytial virus-related infection.

    Science.gov (United States)

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

    2010-08-25

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

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

    Science.gov (United States)

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

    2003-06-30

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

  20. 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.

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

    LENUS (Irish Health Repository)

    Anderson, Evan J

    2017-02-01

    Moderate-late preterm infants, 33-35 weeks\\' gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants.

  2. Burden of Respiratory Syncytial Virus Hospitalizations in Canada

    Directory of Open Access Journals (Sweden)

    Ian Mitchell

    2017-01-01

    Full Text Available Objective. To examine the socioeconomic burden of respiratory syncytial virus (RSV disease for Canadian infants hospitalized for the condition. Data and Methods. The descriptive study used data collected in Alberta, Canada, during 2 consecutive RSV seasons. Infants (<1 year of age were included if they had not received palivizumab and were hospitalized with a confirmed diagnosis of RSV. Hospitalization resource use and parental time burden, out-of-pocket costs, lost work productivity, and stress and anxiety were assessed. Results. 13.4% of all infants (n = 67 had intensive care unit (ICU admission, and average ICU stay for these infants was 6.5 days. Families had average out-of-pocket expenses of 736.69 Canadian dollars (CAD $, and the average time both parents spent in hospital was nearly 7 days (164.0 hours. For working parents (n = 43, average absenteeism was 49% and overall work impairment was 77.8%. Parents also exhibited significant parental stress (3.6 on the Parental Stressor Scale: 43.9 state anxiety and 36.9 trait anxiety scores. Conclusions. Results indicate a high burden associated with the hospitalization of an infant due to RSV disease in terms of resource use, time, productivity, costs, and stress, even among a population of infants not considered to be at risk for the condition.

  3. Respiratory syncytial virus tracking using internet search engine data.

    Science.gov (United States)

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

    2018-04-03

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

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

    International Nuclear Information System (INIS)

    Hirayama, K.; Sakazaki, Hiromi; Murakami, Seiko; Yonezawa, Sumiko; Fujimoto, Keiji; Seto, Toshiyuki; Tanaka, Katsuji; Hattori, Hideji; Matsuoka, Osamu; Murata, Ryosuke

    1999-01-01

    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.)

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

    Science.gov (United States)

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

    2009-10-30

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

  6. 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

  7. Febrile status epilepticus due to respiratory syncytial virus infection.

    Science.gov (United States)

    Uda, Kazuhiro; Kitazawa, Katsuhiko

    2017-08-01

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

  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. Bovine respiratory syncytial virus : immunopathology and vaccine evaluation

    NARCIS (Netherlands)

    Antonis, A.F.G.

    2010-01-01

    Human and bovine RSVs cause severe disease in humans and in cattle respectively. They have been recognised as important respiratory pathogens in the last five decades, and this has resulted in significant research activities on the pathogenesis and intervention strategies around the world.

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

    Science.gov (United States)

    Reina, Jordi; López, Carla

    2013-08-17

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

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

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Olszewska, Wieslawa; Stryhn, Anette

    2004-01-01

    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......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...... 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...

  12. Characterization of the CD8(+)T cell responses directed against respiratory syncytial virus during primary and secondary infection in C57BL/6 mice

    NARCIS (Netherlands)

    Lukens, M.V.; Claassen, E.A.W.; Graaff, de P.M.A.; Dijk, van M.E.A.; Hoogerhout, P.; Toebes, M.; Schumacher, T.N.; Most, van der R.G.; Kimpen, J.L.L.; Bleek, van G.M.

    2006-01-01

    The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4+ and CD8+ T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse

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

    NARCIS (Netherlands)

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

    2017-01-01

    Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related

  14. Reduced Expression of HLA-DR on Monocytes During Severe Respiratory Syncytial Virus Infections

    NARCIS (Netherlands)

    Ahout, I.M.L.; Jans, J.; Haroutiounian, L.; Simonetti, E.R.; Gaast-de Jongh, C.E. van der; Diavatopoulos, D.A.; Jonge, M.I. de; Groot, R. de; Ferwerda, G.

    2016-01-01

    BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants with a wide spectrum of disease severity. Besides environmental and genetic factors, it is thought that the innate immune system plays a pivotal role. The aim of this study was to investigate the expression

  15. 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...

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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.)

  17. 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...

  18. 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.

  19. 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 ...

  20. Influenza and Respiratory Syncytial viral infections in Malaysia: Demographic and Clinical perspective.

    Science.gov (United States)

    Rahman, M M; Wong, K K; Hanafiah, A; Isahak, I

    2014-01-01

    Respiratory infections represent a major public health problem worldwide. The study aimed to determine the prevalence of respiratory syncytial and influenza virus infections and analyzed in respect to demography and clinical perspective. Methods : The specimens were processed by cell culture and immunofluorescent assay (IFA) and real-time reverse transcriptase-PCR (rRT-PCR) for detection of respiratory viruses. Results : Out of 505 specimens 189 (37.8%) were positive, in which RSV was positive in 124(24.8%) cases and influenza A was positive in 65(13%) cases. Positive cases for influenza virus A and RSV were analyzed based on demography: age, gender, ethnicity and clinical symptoms. There were no significant differences among gender, ethnicity and clinical symptoms in both RSV and influenza A virus infections. It was observed that children below 3 years of ages were more prone to RSV infections. On the contrary, influenza virus A infected all age groups of humans. RSV infects mostly child below 3 years of age and influenza virus infects all age group. No specificity of RSV and influenza infection in relation to demography.

  1. 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.

  2. 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.

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

    Science.gov (United States)

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

    2017-10-01

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

  4. 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.

  5. 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.

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

    Science.gov (United States)

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

    2011-01-01

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

  7. 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

    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...... 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...

  8. Peroxisome proliferator-activated receptor-γ agonists inhibit the replication of respiratory syncytial virus (RSV) in human lung epithelial cells

    International Nuclear Information System (INIS)

    Arnold, Ralf; Koenig, Wolfgang

    2006-01-01

    We have previously shown that peroxisome proliferator-activated receptor-γ (PPARγ) agonists inhibited the inflammatory response of RSV-infected human lung epithelial cells. In this study, we supply evidence that specific PPARγ agonists (15d-PGJ 2 , ciglitazone, troglitazone, Fmoc-Leu) efficiently blocked the RSV-induced cytotoxicity and development of syncytia in tissue culture (A549, HEp-2). All PPARγ agonists under study markedly inhibited the cell surface expression of the viral G and F protein on RSV-infected A549 cells. This was paralleled by a reduced cellular amount of N protein-encoding mRNA determined by real-time RT-PCR. Concomitantly, a reduced release of infectious progeny virus into the cell supernatants of human lung epithelial cells (A549, normal human bronchial epithelial cells (NHBE)) was observed. Similar results were obtained regardless whether PPARγ agonists were added prior to RSV infection or thereafter, suggesting that the agonists inhibited viral gene expression and not the primary adhesion or fusion process

  9. Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33.

    Directory of Open Access Journals (Sweden)

    Jordy Saravia

    2015-10-01

    Full Text Available Respiratory syncytial virus (RSV is the most common cause of infant hospitalizations and severe RSV infections are a significant risk factor for childhood asthma. The pathogenic mechanisms responsible for RSV induced immunopathophysiology remain elusive. Using an age-appropriate mouse model of RSV, we show that IL-33 plays a critical role in the immunopathogenesis of severe RSV, which is associated with higher group 2 innate lymphoid cells (ILC2s specifically in neonates. Infection with RSV induced rapid IL-33 expression and an increase in ILC2 numbers in the lungs of neonatal mice; this was not observed in adult mice. Blocking IL-33 with antibodies or using an IL-33 receptor knockout mouse during infection was sufficient to inhibit RSV immunopathogenesis (i.e., airway hyperresponsiveness, Th2 inflammation, eosinophilia, and mucus hyperproduction; whereas administration of IL-33 to adult mice during RSV infection was sufficient to induce RSV disease. Additionally, elevated IL-33 and IL-13 were observed in nasal aspirates from infants hospitalized with RSV; these cytokines declined during convalescence. In summary, IL-33 is necessary, either directly or indirectly, to induce ILC2s and the Th2 biased immunopathophysiology observed following neonatal RSV infection. This study provides a mechanism involving IL-33 and ILC2s in RSV mediated human asthma.

  10. 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.

  11. 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.

  12. 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.

  13. Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis.

    Science.gov (United States)

    Yoshida, Shuichiro; Noguchi, Atsuko; Kikuchi, Wataru; Fukaya, Hiroshi; Igarashi, Kiyoshi; Takahashi, Tsutomu

    2017-12-01

    Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

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

    African Journals Online (AJOL)

    ... A and B and influenza virus types A and B in community-acquired pneumonia by ... It is impossible to distinguish the cause of viral respiratory infections by their ... and pathogen-specific technique of multiplex RT-PCR in order to accomplish ...

  15. 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.

  16. [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

  17. 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.

  18. High Incidence of Recurrent Wheeze in Children With Down Syndrome With and Without Previous Respiratory Syncytial Virus Lower Respiratory Tract Infection

    NARCIS (Netherlands)

    Bloemers, B.; van Furth, A.M.; Weijerman, M.E.; Gemke, R.J.B.J.; Broers, C.J.M.; Kimpen, J.L.L.; Bont, L.

    2010-01-01

    Background: Respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) is associated with the subsequent development of recurrent wheeze. In a recent study, we found a high incidence (9.9%) of hospitalization for RSV-induced LRTI among children with Down syndrome (DS),

  19. 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

    NARCIS (Netherlands)

    Shi, Ting; McAllister, David A.; O'Brien, Katherine L.; Simoes, Eric A. F.; Madhi, Shabir A.; Gessner, Bradford D.; Polack, Fernando P.; Balsells, Evelyn; Acacio, Sozinho; Aguayo, Claudia; Alassani, Issifou; Ali, Asad; Antonio, Martin; Awasthi, Shally; Awori, Juliet O.; Azziz-Baumgartner, Eduardo; Baggett, Henry C.; Baillie, Vicky L.; Balmaseda, Angel; Barahona, Alfredo; Basnet, Sudha; Bassat, Quique; Basualdo, Wilma; Bigogo, Godfrey; Bont, Louis; Breiman, Robert F.; Brooks, W. Abdullah; Broor, Shobha; Bruce, Nigel; Bruden, Dana; Buchy, Philippe; Campbell, Stuart; Carosone-Link, Phyllis; Chadha, Mandeep; Chipeta, James; Chou, Monidarin; Clara, Wilfrido; Cohen, Cheryl; de Cuellar, Elizabeth; Dang, Duc Anh; Dash-yandag, Budragchaagiin; Deloria-Knoll, Maria; Dherani, Mukesh; Eap, Tekchheng; Ebruke, Bernard E.; Echavarria, Marcela; de Freitas Lázaro Emediato, Carla Cecília; Fasce, Rodrigo A.; Feikin, Daniel R.; Feng, Luzhao; Gentile, Angela; Gordon, Aubree; Goswami, Doli; Goyet, Sophie; Groome, Michelle J; Halasa, Natasha; Hirve, Siddhivinayak; Homaira, Nusrat; Howie, Stephen R.C.; Jara, Jorge; Jroundi, Imane; Kartasasmita, Cissy B.; Khuri-Bulos, Najwa; Kotloff, Karen L.; Krishnan, Anand; Libster, Romina; Lopez, Olga; Lucero, Marilla G.; Lucion, Florencia; Lupisan, Socorro P.; Marcone, Debora N.; McCracken, John P.; Mejia, Mario; Moisi, Jennifer C.; Montgomery, Joel M.; Moore, David P.; Moraleda, Cinta; Moyes, Jocelyn; Munywoki, Patrick; Mutyara, Kuswandewi; Nicol, Mark P.; Nokes, D. James; Nymadawa, Pagbajabyn; da Costa Oliveira, Maria Tereza; Oshitani, Histoshi; Pandey, Nitin; Paranhos-Baccalà, Gláucia; Phillips, Lia N.; Picot, Valentina Sanchez; Rahman, Mustafizur; Rakoto-Andrianarivelo, Mala; Rasmussen, Zeba A.; Rath, Barbara A.; Robinson, Annick; Romero, Candice; Russomando, Graciela; Salimi, Vahid; Sawatwong, Pongpun; Scheltema, Nienke; Schweiger, Brunhilde; Scott, J. Anthony G.; Seidenberg, Phil; Shen, Kunling; Singleton, Rosalyn; Sotomayor, Viviana; Strand, Tor A.; Sutanto, Agustinus; Sylla, Mariam; Tapia, Milagritos D.; Thamthitiwat, Somsak; Thomas, Elizabeth D.; Tokarz, Rafal; Turner, Claudia; Venter, Marietjie; Waicharoen, Sunthareeya; Wang, Jianwei; Watthanaworawit, Wanitda; Yoshida, Lay Myint; Yu, Hongjie; Zar, Heather J.; Campbell, Harry; Nair, Harish

    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

  20. 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.

  1. [Quantitative fluorogenic real-time PCR assay for respiratory syncytial virus detection].

    Science.gov (United States)

    Zhang, Qi-wei; You, Shang-you; Sun, Ji-min; Wu, Qi; Yu, Chun-hua; Zhang, Chu-yu

    2005-07-01

    To Establish a rapid and objective quantitative fluorogenic real-time PCR assay for early detection of human respiratory syncytial virus (hRSV). Two pairs of primers and one TaqMan Fluorogenic probe that are specific for the recognition of the most conservative N gene of hRSV for virus detection with LighCycler PCR in 93 nasopharyngeal secretion specimens collected from infants and young children. The assay was compared with virus isolation, routine PCR, nested PCR, and enzyme-linked immunosorbent assay (ELISA). This TaqMan assay had a sensitivity of 1 x 10(2) cDNA copies/microl with a dynamic range between 1 x 10(2) and 1 x 10(7) cDNA copies/microl, which was the same as that of nested PCR, but 10 times more sensitive than routine PCR. The specificity of the assay was evaluated by comparing hRSV with polivirus type 1, coxsackie virus type 2, influenza A, influenza B and adenovirus type 7. A PCR product of the expected size (195 bp) was produced and fluorescence signal detected for hRSV, but not for any of the other viruses. The results in LightCycler and Rotor-Gene instrument were consistent. Forty-four specimens (43.9%) were hRSV-positive with this assay and 4 (4/93,4.3%) were hRSV-positive with ELISA, showing rather low correlation between the two methods. No visible relation was found between the concentration of hRSV RNA and severity of the disease. This assay is rapid, sensitive, specific and quantitative, and has the potential of wide application for early diagnosis of hRSV infection and evaluation of the therapeutic effect.

  2. Characterization of a viral phosphoprotein binding site on the surface of the respiratory syncytial nucleoprotein.

    Science.gov (United States)

    Galloux, Marie; Tarus, Bogdan; Blazevic, Ilfad; Fix, Jenna; Duquerroy, Stéphane; Eléouët, Jean-François

    2012-08-01

    The human respiratory syncytial virus (HRSV) genome is composed of a negative-sense single-stranded RNA that is tightly associated with the nucleoprotein (N). This ribonucleoprotein (RNP) complex is the template for replication and transcription by the viral RNA-dependent RNA polymerase. RNP recognition by the viral polymerase involves a specific interaction between the C-terminal domain of the phosphoprotein (P) (P(CTD)) and N. However, the P binding region on N remains to be identified. In this study, glutathione S-transferase (GST) pulldown assays were used to identify the N-terminal core domain of HRSV N (N(NTD)) as a P binding domain. A biochemical characterization of the P(CTD) and molecular modeling of the N(NTD) allowed us to define four potential candidate pockets on N (pocket I [PI] to PIV) as hydrophobic sites surrounded by positively charged regions, which could constitute sites complementary to the P(CTD) interaction domain. The role of selected amino acids in the recognition of the N-RNA complex by P was first screened for by site-directed mutagenesis using a polymerase activity assay, based on an HRSV minigenome containing a luciferase reporter gene. When changed to Ala, most of the residues of PI were found to be critical for viral RNA synthesis, with the R132A mutant having the strongest effect. These mutations also reduced or abolished in vitro and in vivo P-N interactions, as determined by GST pulldown and immunoprecipitation experiments. The pocket formed by these residues is critical for P binding to the N-RNA complex, is specific for pneumovirus N proteins, and is clearly distinct from the P binding sites identified so far for other nonsegmented negative-strand viruses.

  3. BOVINE RESPIRATORY SYNCYTIAL VIRUS EPIDEMIOLOGY AND RISK FACTORS ON CATTLE HERDS OF CAMPECHE STATE, MEXICO

    Directory of Open Access Journals (Sweden)

    Lisandro Alberto Encalada Mena

    2016-12-01

    Full Text Available High seroprevalence in Yucatan and proximity to the state of Campeche make it necessary to determine the seroprevalence and risk factors of bovine respiratory syncytial virus (VRSB in the state of Campeche, Mexico. Thus the objective of the present work was to determine the seroprevalence and risk factors bovine respiratory syncytial virus (BRSV of the state of Campeche, Mexico. The sampled of 36 cattle herds (842 sera were analyzed by indirect ELISA kit, in the 11 municipalities of Campeche. A survey to obtain risk factors (sex, age of animals, number of animals grazing density, management system, presence of sheep on the farm and access to the roadside was applied and calculated X2 for each variable considered. Of the total number of samples analyzed (842, 273 were positive (32.47%. The prevalence ranges found ranged from 0% to 84%, so in 9 of the herds there were no positive samples, indicating a 75% (27/36 of dispersion of this virus. X2 analysis indicated that all variables were significant and are risk factors regarding with respect to the variable seroprevalence of BRSV. The results indicate a wide circulation of BRSV and we suggest implement recommendations that will enable a lower spread of this virus in the cattle population.

  4. 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.

  5. 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

    consistent, supporting a unidimensional scale structure. Test-retest reliabilities for the percentage of SFD and CSS were above the recommended cut point of 0.70. Cross-sectional and longitudinal correlations were sizeable and statistically significant, demonstrating construct validity. Hypothesized known......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...... the 4-week treatment period of the reported prospective, placebo-controlled trial of montelukast for treatment of postacute RSV were used to assess reliability (internal consistency and test-retest), construct validity (cross-sectional and longitudinal correlations), discriminant validity (known...

  6. Respiratory syncytial virus infection facilitates acute colonization of Pseudomonas aeruginosa in mice

    DEFF Research Database (Denmark)

    de Vrankrijker, Angélica M M; Wolfs, Tom F W; Ciofu, Oana

    2009-01-01

    virus infections in facilitating colonization and infection with P. aeruginosa. A study was undertaken to determine whether respiratory syncytial virus (RSV) infection could facilitate the initiation of an acute infection with P. aeruginosa in vivo. Balb/c mice were infected intranasally with P......Pseudomonas aeruginosa causes opportunistic infections in immunocompromised individuals and patients ventilated mechanically and is the major pathogen in patients with cystic fibrosis, in which it causes chronic infections. Epidemiological, in vitro and animal data suggest a role for respiratory....... These results suggest that RSV can facilitate the initiation of acute P. aeruginosa infection without the RSV infection being clinically apparent. This could have implications for treatment strategies to prevent opportunistic P. aeruginosa lung infection....

  7. Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Boyington

    Full Text Available Respiratory syncytial virus (RSV is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F surface glycoprotein-stabilized in the pre-fusion (pre-F conformation by "DS-Cav1" mutations-elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These "head-only" immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent

  8. Live cell imaging of in vitro human trophoblast syncytialization.

    Science.gov (United States)

    Wang, Rui; Dang, Yan-Li; Zheng, Ru; Li, Yue; Li, Weiwei; Lu, Xiaoyin; Wang, Li-Juan; Zhu, Cheng; Lin, Hai-Yan; Wang, Hongmei

    2014-06-01

    Human trophoblast syncytialization, a process of cell-cell fusion, is one of the most important yet least understood events during placental development. Investigating the fusion process in a placenta in vivo is very challenging given the complexity of this process. Application of primary cultured cytotrophoblast cells isolated from term placentas and BeWo cells derived from human choriocarcinoma formulates a biphasic strategy to achieve the mechanism of trophoblast cell fusion, as the former can spontaneously fuse to form the multinucleated syncytium and the latter is capable of fusing under the treatment of forskolin (FSK). Live-cell imaging is a powerful tool that is widely used to investigate many physiological or pathological processes in various animal models or humans; however, to our knowledge, the mechanism of trophoblast cell fusion has not been reported using a live- cell imaging manner. In this study, a live-cell imaging system was used to delineate the fusion process of primary term cytotrophoblast cells and BeWo cells. By using live staining with Hoechst 33342 or cytoplasmic dyes or by stably transfecting enhanced green fluorescent protein (EGFP) and DsRed2-Nuc reporter plasmids, we observed finger-like protrusions on the cell membranes of fusion partners before fusion and the exchange of cytoplasmic contents during fusion. In summary, this study provides the first video recording of the process of trophoblast syncytialization. Furthermore, the various live-cell imaging systems used in this study will help to yield molecular insights into the syncytialization process during placental development. © 2014 by the Society for the Study of Reproduction, Inc.

  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. Respiratory Syncytial Virus (RSV RNA loads in peripheral blood correlates with disease severity in mice

    Directory of Open Access Journals (Sweden)

    Torres Juan

    2010-09-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity. Methods Balb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood. Results RSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes. Conclusions RSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease.

  12. 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

  13. Serological indication for persistence of bovine respiratory syncytial virus in cattle and attempts to detect the virus

    NARCIS (Netherlands)

    Poel, van der W.H.M.; Langedijk, J.P.M.; Kramps, J.A.; Middel, W.G.J.; Brand, A.; Oirschot, van J.T.

    1997-01-01

    To identify putative persistent bovine respiratory syncytial virus (BRSV) infections in cattle, seven cattle that had experienced BRSV infections were treated with corticosteroids for two periods of 5 days. During the 5-day periods and the 3 weeks after treatment, attempts were made to isolate BRSV

  14. GENETIC SUSCEPTIBILITY TO RESPIRATORY SYNCYTIAL VIRUS BRONCHIOLITIS IN PRETERM CHILDREN IS ASSOCIATED WITH AIRWAY REMODELING GENES AND INNATE IMMUNE GENES

    NARCIS (Netherlands)

    Siezen, Christine L. E.; Bont, Louis; Hodemaekers, Hennie M.; Ermers, Marieke J.; Doornbos, Gerda; van't Slot, Ruben; Wijmenga, Ciska; van Hottwelingen, Hans C.; Kimpen, Jan L. L.; Kimman, Tjeerd G.; Hoebee, Barbara; Janssen, Riny

    Prematurity is a risk factor for severe respiratory syncytial virus bronchiolitis. We show that genetic factors in innate immune genes (IFNA13, IFNAR2, STAT2. IL27, NFKBIA, C3, IL1RN, TLR5), in innate and adaptive immunity (IFNG), and in airway remodeling genes (ADAM33 and TGFBR1), affect disease

  15. Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Infants with Chronic Lung Disease

    NARCIS (Netherlands)

    Paes, Bosco; Fauroux, Brigitte; Figueras-Aloy, Josep; Bont, Louis; Checchia, Paul A; Simões, Eric A F; Manzoni, Paolo; 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 third publication covers the risk and burden of RSV

  16. 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.; et al.,

    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

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

    Science.gov (United States)

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

    2018-05-02

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

  18. 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.

  19. Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Megan E Schmidt

    2018-01-01

    Full Text Available Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.

  20. Respiratory Syncytial Virus Pneumonia Treated with Lower-Dose Palivizumab in a Heart Transplant Recipient

    Directory of Open Access Journals (Sweden)

    J. L. Grodin

    2012-01-01

    Full Text Available Respiratory syncytial virus (RSV is an important community-acquired pathogen that can cause significant morbidity and mortality in patients who have compromised pulmonary function, are elderly, or are immunosuppressed. This paper describes a 70-year-old man with a remote history of heart transplantation who presented with signs and symptoms of pneumonia. Chest computed tomography (CT imaging demonstrated new patchy ground glass infiltrates throughout the upper and lower lobes of the left lung, and the RSV direct fluorescence antibody (DFA was positive. The patient received aerosolized ribavirin, one dose of intravenous immunoglobulin, and one dose of palivizumab. After two months of followup, the patient had improved infiltrates on chest CT, improved pulmonary function testing, and no evidence of graft rejection or dysfunction. There are few data on RSV infections in heart transplant patients, but this case highlights the importance of considering this potentially serious infection and introduces a novel method of treatment.

  1. 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......; and asthma is associated with a long-term increased susceptibility for severe RSV disease, suggesting a host factor being responsible for the severe response to RSV infection. This suggests that severe RSV infection and asthma may share a common genetic predisposition and/or environmental exposure....... was increased as much as 6-fold to 8-fold during the first 2 months after RSV hospitalization but was no longer increased 1 year later. Asthma increased the risk of RSV hospitalization by 3-fold, and the risk was not time-dependent. Analyzing these associations on the basis of asthma defined from use of inhaled...

  2. 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.

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

    Science.gov (United States)

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

    2018-03-01

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

  4. 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

    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......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....... It is possible that a quasispecies variant swarm of BRSV persisted in some of the calves in each herd and that a new and different highly fit virus type (master and consensus sequence) became dominant and spread from a single animal in connection with each new outbreak. Based on the high level of diversity...

  5. 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.

  6. Activation of cytokines and NF-kappa B in corneal epithelial cells infected by respiratory syncytial virus: potential relevance in ocular inflammation and respiratory infection

    Directory of Open Access Journals (Sweden)

    Oakes John E

    2004-07-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a major cause of lower respiratory tract infection, claiming millions of lives annually. The virus infects various cells of the respiratory tract as well as resident inflammatory cells such as macrophages. Infection activates a variety of cellular factors such as cytokines and the pro-inflammatory transcription factor, NF-kappa B, all of which are important players in the respiratory disease. However, the exact natural route of RSV infection and its etiology remain relatively unknown. In this paper, we test the hypothesis that human corneal epithelial cells, which constitute the outermost layer of the cornea, can be infected with RSV, and that the infection leads to the activation of proinflammatory macromolecules. Results Corneal swabs obtained from pediatric patients with acute respiratory disease were found to contain RSV at a high frequency (43 positive out of 72 samples, i.e., 60%. Primary corneal epithelial cells in tissue culture supported robust infection and productive growth of RSV. Infection resulted in the activation of TNF-α, IL-6 and sixteen chemokines as well as NF-κB. Three proinflammatory CXC chemokines (MIG, I-TAC, IP-10 underwent the greatest activation. Conclusions The ocular epithelium is readily infected by RSV. The pro-inflammatory cytokines are likely to play critical roles in the etiology of inflammation and conjunctivitis commonly seen in pediatric patients with respiratory infections. RSV-eye interactions have important implications in RSV transmission, immunopathology of RSV disease, and in the management of conjunctivitis.

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

    Science.gov (United States)

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

    2018-03-01

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

  8. Detection of an untyped strain of bovine respiratory syncytial virus in a dairy herd

    Directory of Open Access Journals (Sweden)

    Ingrid Bortolin Affonso

    2014-10-01

    Full Text Available Bovine respiratory syncytial virus (BRSV causes important lower respiratory tract illness in calves. According to F and G proteins genetic sequences, three BRSV subgroups have been reported and characterized in several countries, showing differences in its distribution. In Brazil, the virus is widely disseminated throughout the herds and the few characterized isolates revealed the solely occurrence of the subgroup B. This study describes the detection and characterization of an untyped BRSV strain from a twenty-days-old calf from a herd without clinical respiratory disease. Nasal swabs were analyzed by RT-nested PCR for the F and G proteins genes. One sample has amplified the F protein gene. Sequencing and subsequent phylogenetic reconstruction were accomplished, revealing that the strain could not be grouped with any other BRSV subgroups reported. This result may suggest that the BRSV is in constantly evolution, even in Brazil, where the vaccination is not a common practice. More detailed studies about BRSV characterization are necessary to know the virus subgroups distribution among the Brazilian herds to recommend appropriated immunoprophylaxis.

  9. 2'-5'-Oligoadenylate Synthetase-Like Protein Inhibits Respiratory Syncytial Virus Replication and Is Targeted by the Viral Nonstructural Protein 1.

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy.

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    Helen Y Chu

    Full Text Available Respiratory syncytial virus (RSV is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described.Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction.RSV was detected in 14 (0.4% illness episodes in 3693 women over 3554 person-years of surveillance from 2011-2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50% women sought care for RSV illness; none died. Of the 7 (50% illness episodes during pregnancy, all had live births with 2 (29% preterm births and a median birthweight of 3060 grams. This compares to 469 (13% preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57% of their infants.RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.

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

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    Wendy Fonseca

    2018-02-01

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

  13. 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.

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

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    Flávio da Silva Mesquita

    2017-05-01

    Full Text Available 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. Resumo: Objetivo: Avaliar o teste QuickVue® RSV Test Kit (QUIDEL Corp, CA, EUA para o diagn

  15. 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

  16. Epidemiology of respiratory syncytial virus-associated acute lower respiratory tract infection hospitalizations among HIV-infected and HIV-uninfected South African children, 2010-2011.

    Science.gov (United States)

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

    2013-12-15

    There are limited data on respiratory syncytial virus (RSV) infection among children in settings with a high prevalence of human immunodeficiency virus (HIV). We studied the epidemiology of RSV-associated acute lower respiratory tract infection (ALRTI) hospitalizations among HIV-infected and HIV-uninfected children in South Africa. Children aged infection among HIV-infected and uninfected children were examined. The relative risk of hospitalization in HIV-infected and HIV-uninfected children was calculated in 1 site with population denominators. Of 4489 participants, 4293 (96%) were tested for RSV, of whom 1157 (27%) tested positive. With adjustment for age, HIV-infected children had a 3-5-fold increased risk of hospitalization with RSV-associated ALRTI (2010 relative risk, 5.6; [95% confidence interval (CI), 4.5-6.4]; 2011 relative risk, 3.1 [95% CI, 2.6-3.6]). On multivariable analysis, HIV-infected children with RSV-associated ALRTI had higher odds of death (adjusted odds ratio. 31.1; 95% CI, 5.4-179.8) and hospitalization for >5 days (adjusted odds ratio, 4.0; 95% CI, 1.5-10.6) than HIV-uninfected children. HIV-infected children have a higher risk of hospitalization with RSV-associated ALRTI and a poorer outcome than HIV-uninfected children. These children should be targeted for interventions aimed at preventing severe RSV disease.

  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. Epidemiological and molecular surveillance of influenza and respiratory syncytial viruses in children with acute respiratory infections (2004/2005 season

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    Alessandra Zappa

    2008-03-01

    Full Text Available Objective. During the 2004/2005 influenza season an active virological surveillance of influenza viruses and respiratory syncytial virus (RSV was carried out to monitor the epidemiologic trend of acute respiratory infections (ARI in the paediatric community. Materials and methods. 100 patients (51 males, 49 females; mean age: 19 months, either treated at the Emergency Unit or hospitalized in the Pediatric Unit of “San Carlo Borromeo Hospital” (Milan, reporting symptoms related to ARI were enrolled. Pharyngeal swabs were collected for virological investigation by: 1 multiplexnested- PCR for the simultaneous identification of both influenza A and B viruses and RSV; 2 multiplex-nested- PCR for the subtyping of influenza A viruses (H1 and H3. Results. 12% (12/100 subjects were infected with influenza A virus, 4% (4/100 with influenza B virus and 14 (14% with RSV. Of all the 12 influenza A positive samples 4 (33.3% belonged to subtype H1 and 8 (66.7% to subtype H3. Bronchiolitis and bronchitis episodes were significantly higher among RSV-infected subjects than among influenza- infected subjects (42.8% vs 6.2%; p<0.05 and 35.7% vs 6.2%; p<0.05, respectively. Pneumonia episodes occurred similarly both in influenza-infected children and in RSV-infected ones. Conclusions. During the 2004/2005 influenza season, influenza viruses and RSV were liable for high morbidity among paediatric subjects.The present study underlies the importance of planning an active surveillance of respiratory viral infections among paediatric cases requiring hospitalization due to ARI.A thorough analysis of target population features, of viruses antigenic properties and seasonality will be decisive in the evaluation of each clinical event.

  19. Antibody Tracing, Seroepidemiology and Risk Factors of Bovine Respiratory Syncytial Virus and Bovine Adenovirus-3 in Dairy Holstein Farms

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    Mahsa FARZINPOUR

    2016-01-01

    Full Text Available Antibody tracing, risk factors and seroepidemiology of bovine respiratory syncytial virus and bovine adenovirus-3 were investigated in 22 Industrial and Semi-Industrial dairy Holstein farms. Serum samples (n=736 from various ages of unvaccinated cows were collected from May to September 2012. Risk factors including age, past history of respiratory diseases, amount of milk production, husbandry type and herd size were considered. Data were analyzed by Chi-square and logistic regression. Results indicated that the infection with some of individual viruses was related to past history of respiratory disease and herd size. No specific pattern was seen on the effect of level of milk production on seropositivity of animals. The seroprevalence for BRSV and BAV-3 were 89.1% and 88%, respectively. The present study indicates that infections of bovine respiratory viruses frequently occur in cattle of Fars province and the main viral cause of primary occurrence of respiratory diseases may be due to aforementioned viruses.

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

    Science.gov (United States)

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

    1987-01-01

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

  1. The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter.

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    Sarah L Noton

    Full Text Available Respiratory syncytial virus (RSV is an RNA virus in the Family Paramyxoviridae. Here, the activities performed by the RSV polymerase when it encounters the viral antigenomic promoter were examined. RSV RNA synthesis was reconstituted in vitro using recombinant, isolated polymerase and an RNA oligonucleotide template representing nucleotides 1-25 of the trailer complement (TrC promoter. The RSV polymerase was found to have two RNA synthesis activities, initiating RNA synthesis from the +3 site on the promoter, and adding a specific sequence of nucleotides to the 3' end of the TrC RNA using a back-priming mechanism. Examination of viral RNA isolated from RSV infected cells identified RNAs initiated at the +3 site on the TrC promoter, in addition to the expected +1 site, and showed that a significant proportion of antigenome RNAs contained specific nucleotide additions at the 3' end, demonstrating that the observations made in vitro reflected events that occur during RSV infection. Analysis of the impact of the 3' terminal extension on promoter activity indicated that it can inhibit RNA synthesis initiation. These findings indicate that RSV polymerase-promoter interactions are more complex than previously thought and suggest that there might be sophisticated mechanisms for regulating promoter activity during infection.

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

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    Reimers, Kerstin [Klinik fuer Plastische, Hand-und Wiederherstellungschirurgie, Podbielskistrasse 380, D-30659 Hannover (Germany); Buchholz, Katja [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany); Werchau, Hermann [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany)

    2005-01-20

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

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

    International Nuclear Information System (INIS)

    Alsuwaidi, Ahmed R.; Albawardi, Alia; Almarzooqi, Saeeda; Benedict, Sheela; Othman, Aws R.; Hartwig, Stacey M.; Varga, Steven M.; Souid, Abdul-Kader

    2014-01-01

    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 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

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

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    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.

  5. A review of palivizumab and emerging therapies for respiratory syncytial virus.

    Science.gov (United States)

    Shadman, Kristin A; Wald, Ellen R

    2011-11-01

    Respiratory syncytial virus (RSV) is an important pathogen in children and adults; however, current treatment options are primarily supportive. Palivizumab, the only approved specific monoclonal antibody for RSV is used prophylactically to reduce morbidity in a select population of high-risk children. The development and current use of palivizumab; the potential role of palivizumab as preventive therapy in patients with cystic fibrosis, asthma and compromised immune systems; and explores the limited research in which palivizumab has been used for treatment of RSV. The modified recommendations for the use of palivizumab espoused by the American Academy of Pediatrics and research on the cost-effectiveness of this product are presented. In addition, the authors discuss the development of enhanced monoclonal antibodies including motavizumab, which was recently denied FDA approval for preventative therapy. The authors explore the historical and current efforts to develop a vaccine targeting RSV. The current status of antiviral drug development is also reviewed. The literature search included RSV-Ig, palivizumab, and emerging drugs and vaccines for the treatment of RSV as keywords and titles from 1997 to 2011. Although there are potential drugs and vaccines in development to prevent or reduce the effects of RSV infection, palivizumab remains the only licensed product to reduce the severity of disease in high-risk pediatric patients.

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

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    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.

  7. Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma

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    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.

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

    Science.gov (United States)

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

    2014-08-30

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

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

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    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

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

    Science.gov (United States)

    Walsh, Paul; Behrens, Nicole; Carvallo Chaigneau, Francisco R.; McEligot, Heather; Agrawal, Karan; Newman, John W.; Anderson, Mark; Gershwin, Laurel J.

    2016-01-01

    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 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. Hypotheses 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. Methods 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. Results One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (pibuprofen 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. Conclusions Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes. However lung

  11. Respiratory syncytial virus-related encephalitis: magnetic resonance imaging findings with diffusion-weighted study

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    Park, Arim; Suh, Sang-il; Seol, Hae-Young; Son, Gyu-Ri; Lee, Nam-Joon; Lee, Young Hen; Seo, Hyung Suk; Eun, Baik-Lin

    2014-01-01

    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.)

  12. Respiratory syncytial virus-related encephalitis: magnetic resonance imaging findings with diffusion-weighted study

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    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.)

  13. Severe respiratory syncytial virus bronchiolitis in infants is associated with reduced airway interferon gamma and substance P.

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    Malcolm G Semple

    2007-10-01

    Full Text Available Severe human respiratory syncytial virus (hRSV bronchiolitis in previously well infants may be due to differences in the innate immune response to hRSV infection.to determine if factors mediating proposed mechanisms for severe bronchiolitis differ with severity of disease.197 infants admitted to hospital with hRSV bronchiolitis were recruited and grouped according to no oxygen requirement (n = 27, oxygen dependence (n = 114 or mechanical ventilation (n = 56. We collected clinical data, nasopharyngeal aspirate (NPA and if ventilated bronchoalveolar lavage (BAL. Interferon-gamma (IFN-gamma, substance P (SP, interleukin 9 (IL-9, urea and hRSV load, were measured in cell free supernatant from NPA and BAL. Multivariate analysis compared independent effects of clinical, virological and immunological variables upon disease severity. IFN-gamma and SP concentrations were lower in NPA from infants who required oxygen or mechanical ventilation. Viral load and IL-9 concentrations were high but did not vary with severity of disease. Independent predictors of severe disease (in diminishing size of effect were low weight on admission, low gestation at birth, low NPA IFN-gamma and NPA SP. Nasal airway sampling appears to be a useful surrogate for distal airway sampling since concentrations of IFN-gamma, SP, IL-9 and viral load in NPA correlate with the same in BAL.Our data support two proposed mechanisms for severe hRSV disease; reduced local IFN-gamma response and SP mediated inflammation. We found large amounts of hRSV and IL-9 in airways secretions from the upper and lower respiratory tract but could not associate these with disease severity.

  14. Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine Triphosphate.

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    Jerome Deval

    2015-06-01

    Full Text Available Respiratory syncytial virus (RSV causes severe lower respiratory tract infections, yet no vaccines or effective therapeutics are available. ALS-8176 is a first-in-class nucleoside analog prodrug effective in RSV-infected adult volunteers, and currently under evaluation in hospitalized infants. Here, we report the mechanism of inhibition and selectivity of ALS-8176 and its parent ALS-8112. ALS-8176 inhibited RSV replication in non-human primates, while ALS-8112 inhibited all strains of RSV in vitro and was specific for paramyxoviruses and rhabdoviruses. The antiviral effect of ALS-8112 was mediated by the intracellular formation of its 5'-triphosphate metabolite (ALS-8112-TP inhibiting the viral RNA polymerase. ALS-8112 selected for resistance-associated mutations within the region of the L gene of RSV encoding the RNA polymerase. In biochemical assays, ALS-8112-TP was efficiently recognized by the recombinant RSV polymerase complex, causing chain termination of RNA synthesis. ALS-8112-TP did not inhibit polymerases from host or viruses unrelated to RSV such as hepatitis C virus (HCV, whereas structurally related molecules displayed dual RSV/HCV inhibition. The combination of molecular modeling and enzymatic analysis showed that both the 2'F and the 4'ClCH2 groups contributed to the selectivity of ALS-8112-TP. The lack of antiviral effect of ALS-8112-TP against HCV polymerase was caused by Asn291 that is well-conserved within positive-strand RNA viruses. This represents the first comparative study employing recombinant RSV and HCV polymerases to define the selectivity of clinically relevant nucleotide analogs. Understanding nucleotide selectivity towards distant viral RNA polymerases could not only be used to repurpose existing drugs against new viral infections, but also to design novel molecules.

  15. Effects of formalin-inactivated respiratory syncytial virus (FI-RSV in the perinatal lamb model of RSV.

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    Rachel J Derscheid

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

  16. Role of Bibersteinia trehalosi, respiratory syncytial virus, and parainfluenza-3 virus in bighorn sheep pneumonia.

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    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Subramaniam, Renuka; Herndon, Caroline N; Bavananthasivam, Jegarubee; Haldorson, Gary J; Foreyt, William J; Evermann, James F; Herrmann-Hoesing, Lynn M; Knowles, Donald P; Srikumaran, Subramaniam

    2013-02-22

    Pneumonic bighorn sheep (BHS) have been found to be culture- and/or sero-positive for Bibersteinia trehalosi, respiratory syncytial virus (RSV), and parainfluenza-3 virus (PI-3). The objective of this study was to determine whether these pathogens can cause fatal pneumonia in BHS. In the first study, two groups of four BHS each were intra-tracheally administered with leukotoxin-positive (Group I) or leukotoxin-negative (Group II) B. trehalosi. All four animals in Group I developed severe pneumonia, and two of them died within 3 days. The other two animals showed severe pneumonic lesions on euthanasia and necropsy. Animals in Group II neither died nor showed gross pneumonic lesions on necropsy, suggesting that leukotoxin-positive, but not leukotoxin-negative, B. trehalosi can cause fatal pneumonia in BHS. In the second study, two other groups of four BHS (Groups III and IV) were intra-nasally administered with a mixture of RSV and PI-3. Four days later, RSV/PI-3-inoculated Group IV and another group of four BHS (Group V, positive control) were intra-nasally administered with Mannheimia haemolytica, the pathogen that consistently causes fatal pneumonia in BHS. All four animals in group III developed pneumonia, but did not die during the study period. However all four animals in Group IV, and three animals in Group V developed severe pneumonia and died within two days of M. haemolytica inoculation. The fourth animal in Group V showed severe pneumonic lesions on euthanasia and necropsy. These findings suggest that RSV/PI-3 can cause non-fatal pneumonia, but are not necessary predisposing agents for M. haemolytica-caused pneumonia of BHS. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

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    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.

  18. Exposure of neonates to Respiratory Syncytial Virus is critical in determining subsequent airway response in adults

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    Daly Melissa

    2006-08-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma. Methods To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 × 105 TCID50/g body weight and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined. Results RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-α levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV. Conclusion Neonatal RSV exposure results in long term

  19. [Respiratory syncytial virus outbreak in a tertiary hospital Neonatal Intensive Care Unit].

    Science.gov (United States)

    Moreno Parejo, Carlos; Morillo García, Aurea; Lozano Domínguez, Carmen; Carreño Ochoa, Concepción; Aznar Martín, Javier; Conde Herrera, Manuel

    2016-09-01

    Investigation and control of a respiratory syncytial virus (RSV) outbreak that affected the Neonatal Intensive Care Unit (NICU) of a university hospital from October to December 2012. Cohort study of children admitted to the NICU. The infection attack rate was calculated. A descriptive analysis of the cases and a multivariate analysis was performed using the variables that were shown to be risk factors for RSV infection. Preventive measures taken were: contact isolation; hand hygiene training and observation; exclusivity of a health team of nurses and physicians for positive cases, restrictions on visitor numbers; surveillance RSV testing, and palivizumab prophylaxis. The outbreak had three epidemic waves and 20 positive cases out of a total of 48 children admitted. The overall attack rate was 42%. Half of positive cases were children, with a median age of 36 days (p25=22, p75=58). The independent risk factors for RSV infection were birth weight below 1000 grams (OR=23.5; P=.002) and to have another nosocomial infection the week before the diagnosis of RSV infection (OR=19.98; P=.016). It was an outbreak with a high number of cases, due to the delay in notification, prolonged RSV carrier status, and low adherence to hand hygiene practice, which favoured the cross-transmission of infection. The most effective preventive measures were direct observation of hand hygiene and supervision of isolation measures. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

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    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.

  1. Development and clinical applications of novel antibodies for prevention and treatment of respiratory syncytial virus infection.

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    Mejias, Asuncion; Garcia-Maurino, Cristina; Rodriguez-Fernandez, Rosa; Peeples, Mark E; Ramilo, Octavio

    2017-01-11

    Respiratory syncytial virus (RSV) remains a significant cause of morbidity and mortality in infants and young children, immunocompromised patients and the elderly. Despite the high disease burden, an effective and safe vaccine is lacking, although several candidates are currently in development. Current treatment for RSV infection remains largely supportive and RSV-specific options for prophylaxis are limited to palivizumab. In the past few years, novel therapeutic options including nanobodies, polyclonal and monoclonal antibodies have emerged and there are several products in preclinical and Phase-I, -II or -III clinical trials. The major target for antiviral drug development is the surface fusion (F) glycoprotein, which is crucial for the infectivity and pathogenesis of the virus. Solving the structures of the two conformations of the RSV F protein, the prefusion and postfusion forms, has revolutionized RSV research. It is now known that prefusion F is highly superior in inducing neutralizing antibodies. In this section we will review the stages of development and availability of different antibodies directed against RSV for the prevention and also for treatment of acute RSV infections. Some of these newer anti-RSV agents have shown enhanced potency, are being explored through alternative routes of administration, have improved pharmacokinetic profiles with an extended half-life, and may reduce design and manufacturing costs. Management strategies will require targeting not only high-risk populations (including adults or immunocompromised patients), but also previously healthy children who, in fact, represent the majority of children hospitalized with RSV infection. Following treated patients longitudinally is essential for determining the impact of these strategies on the acute disease as well as their possible long-term benefits on lung morbidity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Respiratory syncytial virus infections enhance cigarette smoke induced COPD in mice.

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    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.

  3. When to perform urine cultures in respiratory syncytial virus-positive febrile older infants?

    Science.gov (United States)

    Kaluarachchi, Dinushan; Kaldas, Virginia; Erickson, Evelyn; Nunez, Randolph; Mendez, Magda

    2014-09-01

    Respiratory syncytial virus (RSV) infections are associated with clinically significant rate of urinary tract infections (UTIs) in young infants. Previous research investigating RSV infections and UTIs has been performed mainly in infants younger than 2 to 3 months and has not focused on the risk of UTI in infants 3 to 12 months. This study aimed to assess the rate of UTIs in febrile RSV-positive older infants admitted as inpatients and identify predictors of UTI in febrile RSV-positive older infants. This is a retrospective comparative study of febrile RSV-positive infants 0 to 12 months of age admitted to the inpatient pediatric unit of Lincoln Medical and Mental Health Center, Bronx, from September through April 2006 to 2012. Infants 3 to 12 months were considered the cases, and infants 0 to 3 months were the comparative group. The rate of UTIs between the 2 groups was compared. Univariate tests and multiple logistic regression were used to identify demographic/clinical factors associated with UTI in febrile RSV-positive older infants. A total of 414 RSV-positive febrile infants were enrolled including 297 infants 3 to 12 months of age. The rate of UTI in older infants was 6.1% compared with 6.8% in infants younger than 3 months. Positive urinalysis finding was an independent predictor of UTI (P = 0.003) in older infants. All 11 boys with UTI were uncircumcised, and none of the 51 circumcised boys had UTI. Demographic (race, sex, and age) and clinical factors (temperature, white blood cell count, and absolute neutrophil count) were not associated with UTI. Febrile older infants who are RSV positive have a clinically significant rate of UTIs. It seems prudent to examine the urine of these older infants. Positive urinalysis finding was a predictive factor of UTI. Circumcised boys are at a decreased risk of UTI, compared with uncircumcised boys.

  4. Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via Interferon Beta and Indoleamine-2,3-Dioxygenase.

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    Michael B Cheung

    Full Text Available Respiratory syncytial virus (RSV has been reported to infect human mesenchymal stem cells (MSCs but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts. RSV-infected MSCs showed differentially altered expression of cytokines and chemokines such as IL-1β, IL6, IL-8 and SDF-1 compared to epithelial cells. Notably, RSV-infected MSCs exhibited significantly increased expression of IFN-β (~100-fold and indoleamine-2,3-dioxygenase (IDO (~70-fold than in mock-infected MSCs. IDO was identified in cytosolic protein of infected cells by Western blots and enzymatic activity was detected by tryptophan catabolism assay. Treatment of PBMCs with culture supernatants from RSV-infected MSCs reduced their proliferation in a dose dependent manner. This effect on PBMC activation was reversed by treatment of MSCs with the IDO inhibitors 1-methyltryptophan and vitamin K3 during RSV infection, a result we confirmed by CRISPR/Cas9-mediated knockout of IDO in MSCs. Neutralizing IFN-β prevented IDO expression and activity. Treatment of MSCs with an endosomal TLR inhibitor, as well as a specific inhibitor of the TLR3/dsRNA complex, prevented IFN-β and IDO expression. Together, these results suggest that RSV infection of MSCs alters their immune regulatory function by upregulating IFN-β and IDO, affecting immune cell proliferation, which may account for the lack of protective RSV immunity and for chronicity of RSV-associated lung diseases such as asthma and COPD.

  5. Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus

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    Barik Sailen

    2003-05-01

    Full Text Available Abstract Background Actin is required for the gene expression and morphogenesis of respiratory syncytial virus (RSV, a clinically important Pneumovirus of the Paramyxoviridae family. In HEp-2 cells, RSV infection also induces actin stress fibers, which may be important in the immunopathology of the RSV disease. Profilin, a major regulator of actin polymerization, stimulates viral transcription in vitro. Thus, we tested the role of profilin in RSV growth and RSV-actin interactions in cultured cells (ex vivo. Results We tested three cell lines: HEp-2 (human, A549 (human, and L2 (rat. In all three, RSV grew well and produced fused cells (syncytium, and two RSV proteins, namely, the phosphoprotein P and the nucleocapsid protein N, associated with profilin. In contrast, induction of actin stress fibers by RSV occurred in HEp-2 and L2 cells, but not in A549. Knockdown of profilin by RNA interference had a small effect on viral macromolecule synthesis but strongly inhibited maturation of progeny virions, cell fusion, and induction of stress fibers. Conclusions Profilin plays a cardinal role in RSV-mediated cell fusion and viral maturation. In contrast, interaction of profilin with the viral transcriptional proteins P and N may only nominally activate viral RNA-dependent RNA polymerase. Stress fiber formation is a cell-specific response to infection, requiring profilin and perhaps other signaling molecules that are absent in certain cell lines. Stress fibers per se play no role in RSV replication in cell culture. Clearly, the cellular architecture controls multiple steps of host-RSV interaction, some of which are regulated by profilin.

  6. Respiratory syncytial virus groups A and B in Porto Alegre, Brazil, from 1990 to 1995 and 1998

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    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.

  7. Radiographic and radionuclide lung perfusion imaging in healthy calves and calves naturally infected with bovine respiratory syncytial virus

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    Verhoeff, J.; Brom, W.E. van den; Ingh, T.S.G.A.M. van den

    1992-01-01

    Nine calves between three and 18 weeks old with serologically confirmed natural bovine respiratory syncytial virus infection were examined clinically, radiographically and by radionuclide lung perfusion imaging. The results were compared with those from seven healthy calves. The diseased calves were euthanased and examined pathologically, virologically and bacteriologically. The clinical signs indicated that the disease was in an acute stage. Radiography of the diseased animals revealed cysts, corresponding morphologically with bullous emphysema, and infiltrations roughly corresponding in distribution with atelectatic and, or, pneumonic areas. Radionuclide lung perfusion imaging revealed no perfusion shifts between the left and right lungs and a normal perfusion pattern in five of the nine diseased calves. The abnormalities in the perfusion patterns of three calves were probably caused by anatomical disorders such as cysts and pleural adhesions, but no cause of the abnormality could be found in one calf. These findings suggest that in calves infected with bovine respiratory syncytial virus, the normal perfusion pattern is maintained until anatomical disorders occur. The pathological examination and radiography revealed that the cranioventral lung fields were particularly poorly ventilated. This finding and the normal perfusion pattern indicate that these parts of the lungs are probably the sites where shuntings and perfusion-ventilation mismatchings occur

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

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    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

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

    Science.gov (United States)

    Spaeder, M C; Fackler, J C

    2012-04-01

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

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

    Science.gov (United States)

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

    2018-04-16

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

  11. 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...... disease. This model is a valuable tool for the study of the pathogenesis of BRSV and for vaccine efficacy studies....

  12. A bovine respiratory syncytial virus strain with mutations in subgroup-specific antigenic domains of the G protein induces partial heterologous protection in cattle

    NARCIS (Netherlands)

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

    1998-01-01

    Bovine respiratory syncytial virus (BRSV) strains are tentatively divided in subgroups A, AB and B, based on antigenic differences of the G protein. A Dutch BRSV strain (Waiboerhoeve: WBH), could not be assigned to one of the subgroups, because the strain did not react with any monoclonal antibody

  13. An evaluation of the emerging interventions against Respiratory Syncytial Virus (RSV-associated acute lower respiratory infections in children

    Directory of Open Access Journals (Sweden)

    Simões Eric AF

    2011-04-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV is the leading cause of acute lower respiratory infections (ALRI in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results In the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development; moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions; and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost

  14. An evaluation of the emerging interventions against Respiratory Syncytial Virus (RSV)-associated acute lower respiratory infections in children.

    Science.gov (United States)

    Nair, Harish; Verma, Vasundhara R; Theodoratou, Evropi; Zgaga, Lina; Huda, Tanvir; Simões, Eric A F; Wright, Peter F; Rudan, Igor; Campbell, Harry

    2011-04-13

    Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization. We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. In the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development; moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions; and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost; moderate levels of optimism for likelihood of efficacy

  15. FACTORS DETERMINING THE HOSPITALISATION DURATION OF STAY IN CHILDREN WITH SEVERE RESPIRATORY SYNCYTIAL VIRUS (RSV INFECTION IN THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    A.A. Baranov

    2011-01-01

    Full Text Available The epidemiologic data on RSV infection prevalence in the Russian Federation and its impact on respiratory morbidity in the pediatric population are limited. This article provides the analysis of results of a prospective, multicenter, observational cohort study. The study was conducted in 9 centers in the Russian Federation — in Moscow, St. Petersburg, and Tomsk. Children less than 2 years of age were included. It was found that during the season of high RSV morbidity RSV is found in 38 % of children hospitalized for lower respiratory tract infections; mean hospitalisation duration in children with severe RSV infection was over 1 week. Usually the duration of hospitalization was associated with disease severity and requirements for healthcare resources and oxygen supplementation. Moreover, in the Russian Federation the hospital length of stay in patients with RSV infection depended on the type of medical insurance. It was demonstrated that RSV infection caused severe respiratory failure in some infants less than 1 year of age and, therefore, was a substantial burden for the system of hospital medical care in the Russian Federation. Prophylaxis of severe RSV infection in high-risk groups of children during the might reduce the need for hospitalization. Key words: respiratory syncytial virus infection, bronchiolitis, risk factors, prophylaxis, epidemiology, children. (Pediatric pharmacology. — 2011; 8 (6: 61–66.

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

    Directory of Open Access Journals (Sweden)

    Young J. Lee

    2018-01-01

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

  17. Characterization of oligosaccharide structures on a chimeric respiratory syncytial virus protein expressed in insect cell line Sf9

    International Nuclear Information System (INIS)

    Wathen, M.W.; Aeed, P.A.; Elhammer, A.P.

    1991-01-01

    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 [ 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 Galβ1-3GalNAc 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 α1-6 to the asparagine-linked N-acetylglucosamine

  18. Experiments toward the development of a radioimmunoassay for the detection of serum antibodies for the respiratory syncytial virus

    International Nuclear Information System (INIS)

    Heizmann, W.R.

    1982-01-01

    In order to detect an infection by the respiratory syncytial virus (RSV) quickly and safely, a radioimmunassay (RIA) should be developed. Various antigen preparations were compared to one another. The immune serums used in the RIA came from guinea pigs with a RSV antibody titer of up to 320 in the complement binding reaction. A number of observations lead to the discussion of the possibility of the formation (incomplete) of cross-reactive antibodies between virus and host cell. This hypothesis could be well supported through references in the literature. Under the assumption of the existence of cross-reactive antibodies, a further model of the pathogenesis of the RSV illness allows itself to be developed, which could be preceived as an illness with autoimmune components. With this model the varying courses of this disease in different age groups can be easily explained. (orig.) [de

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

    International Nuclear Information System (INIS)

    Brown, Gaie; Jeffree, Chris E.; McDonald, Terence; McL Rixon, Helen W.; Aitken, James D.; Sugrue, Richard J.

    2004-01-01

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

  20. 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

  1. Respiratory syncytial virus fusion glycoprotein expressed in insect cells form protein nanoparticles that induce protective immunity in cotton rats.

    Directory of Open Access Journals (Sweden)

    Gale Smith

    Full Text Available Respiratory Syncytial Virus (RSV is an important viral agent causing severe respiratory tract disease in infants and children as well as in the elderly and immunocompromised individuals. The lack of a safe and effective RSV vaccine represents a major unmet medical need. RSV fusion (F surface glycoprotein was modified and cloned into a baculovirus vector for efficient expression in Sf9 insect cells. Recombinant RSV F was glycosylated and cleaved into covalently linked F2 and F1 polypeptides that formed homotrimers. RSV F extracted and purified from insect cell membranes assembled into 40 nm protein nanoparticles composed of multiple RSV F oligomers arranged in the form of rosettes. The immunogenicity and protective efficacy of purified RSV F nanoparticles was compared to live and formalin inactivated RSV in cotton rats. Immunized animals induced neutralizing serum antibodies, inhibited virus replication in the lungs, and had no signs of disease enhancement in the respiratory track of challenged animals. RSV F nanoparticles also induced IgG competitive for binding of palivizumab neutralizing monoclonal antibody to RSV F antigenic site II. Antibodies to this epitope are known to protect against RSV when passively administered in high risk infants. Together these data provide a rational for continued development a recombinant RSV F nanoparticle vaccine candidate.

  2. Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

    International Nuclear Information System (INIS)

    Morton, Craig J.; Cameron, Rachel; Lawrence, Lynne J.; Lin Bo; Lowe, Melinda; Luttick, Angela; Mason, Anthony; McKimm-Breschkin, Jenny; Parker, Michael W.; Ryan, Jane; Smout, Michael; Sullivan, Jayne; Tucker, Simon P.; Young, Paul R.

    2003-01-01

    Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors

  3. Construction of adenoviral vectors expressing F and G glycoproteins of human respiratory syncytial virus (HRSV Construção de vetores adenovirais expressando as glicoproteínas F e G de vírus respiratório sincicial humano (HRSV

    Directory of Open Access Journals (Sweden)

    Ithana Monteiro Kosaka

    2004-06-01

    Full Text Available Human Respiratory Syncytial Virus (HRSV was first characterized in 1957 and has since been recognized as the most common viral cause of severe respiratory tract infection in young infants worldwide. Despite many years of research there is still no effective treatment or any immediate prospect of a vaccine. The HRSV genome is composed of single stranded negative sense RNA and the virion consists of a nucleocapsid packaged within a lipid envelope. The envelope contains spike-like projections, each being a homo-oligomer of one of three transmembrane viral envelope proteins: the attachment protein G, the fusion protein F involved in viral penetration and the small hydrofobic protein SH. The aim of this work was to construct two recombinant replication-defective adenoviruses carrying separately F and G genes from HRSV. This system was chosen because adenovirus delivers genes into target cells with high efficiency in a variety of cell lines and can be used in vitro and in vivo. In order to obtain the recombinant viruses, we did RT-PCR of RNA extracted from the HRSV A2 strain, the genes F and G were cloned in to pAdeno-X vectors. pAdeno-F and pAdeno-G were transfected in HEK-293 cells for the production of recombinant viruses, that expressed efficiently these two proteins and provide us the means for doing functional assays and immunization tests.O Vírus Sincicial Respiratório Humano (HRSV foi isolado e caracterizado pela primeira vez em 1957 e é considerado como o patógeno viral mais freqüente do trato respiratório de bebês e crianças. Apesar de muitos anos de pesquisa, não há ainda um tratamento específico ou uma vacina licenciada. Seu genoma é composto por uma fita simples de RNA polaridade negativa e o vírion consiste em um nucleocapsídeo empacotado por um envelope lipídico. O envelope contém projeções, chamadas espículas, constituídas de homoligômeros de uma das 3 glicoproteínas de membrana: a proteína de ligação G

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

    Science.gov (United States)

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

    2017-11-01

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

  5. Independent lung ventilation in a newborn with asymmetric acute lung injury due to respiratory syncytial virus: a case report

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    Di Nardo Matteo

    2008-06-01

    Full Text Available Abstract Introduction Independent lung ventilation is a form of protective ventilation strategy used in adult asymmetric acute lung injury, where the application of conventional mechanical ventilation can produce ventilator-induced lung injury and ventilation-perfusion mismatch. Only a few experiences have been published on the use of independent lung ventilation in newborn patients. Case presentation We present a case of independent lung ventilation in a 16-day-old infant of 3.5 kg body weight who had an asymmetric lung injury due to respiratory syncytial virus bronchiolitis. We used independent lung ventilation applying conventional protective pressure controlled ventilation to the less-compromised lung, with a respiratory frequency proportional to the age of the patient, and a pressure controlled high-frequency ventilation to the atelectatic lung. This was done because a single tube conventional ventilation protective strategy would have exposed the less-compromised lung to a high mean airways pressure. The target of independent lung ventilation is to provide adequate gas exchange at a safe mean airways pressure level and to expand the atelectatic lung. Independent lung ventilation was accomplished for 24 hours. Daily chest radiograph and gas exchange were used to evaluate the efficacy of independent lung ventilation. Extubation was performed after 48 hours of conventional single-tube mechanical ventilation following independent lung ventilation. Conclusion This case report demonstrates the feasibility of independent lung ventilation with two separate tubes in neonates as a treatment of an asymmetric acute lung injury.

  6. Clinical and epidemiological aspects related to the detection of adenovirus or respiratory syncytial virus in infants hospitalized for acute lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Eduardo A. Ferone

    2014-01-01

    Full Text Available OBJECTIVE: To characterize and compare clinical, epidemiological, and laboratory aspects ofinfants with acute lower respiratory infection (ALRI associated with the detection of adenovirus(ADV or respiratory syncytial virus (RSV. METHODS: A preliminary respiratory infection surveillance study collected samples of nasopharyngeal aspirate (NPA for viral research, linked to the completion of a standard protocol, from children younger than two years admitted to a university hospital with ALRI, between March of 2008 and August of 2011. Polymerase chain reaction (PCR was used for eight viruses: ADV, RSV, metapneumovirus, Parainfluenza 1, 2, and 3, and Influenza A and B. Cases with NPA collectedduring the first 24 hours of admission, negative results of blood culture, and exclusive detection of ADV (Gadv group or RSV (Grsv group were selected for comparisons. RESULTS: The preliminary study included collection of 1,121 samples of NPA, 813 collected in thefirst 24 hours of admission, of which 50.3% were positive for at least one virus; RSV was identifiedin 27.3% of cases surveyed, and ADV was identified in 15.8%. Among the aspects analyzed inthe Gadv (n = 58 and Grsv (n = 134 groups, the following are noteworthy: the higher meanage, more frequent prescription of antibiotics, and the highest median of total white blood cellcount and C-reactive protein values in Gadv. CONCLUSIONS: PCR can detect persistent/latent forms of ADV, an aspect to be considered wheninterpreting results. Additional studies with quantitative diagnostic techniques could elucidatethe importance of the high frequency observed.

  7. Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders.

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    Nicola Lehners

    Full Text Available Respiratory viruses are a cause of upper respiratory tract infections (URTI, but can be associated with severe lower respiratory tract infections (LRTI in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17% were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111 underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic. LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1pdm09, A(H3N2, influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75% of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01 and was most pronounced in patients with RSV infection (n = 16 with a median duration of viral shedding for 80 days (range 35-334 days. Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for

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

    Science.gov (United States)

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

    2015-04-01

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

  9. Virucidal activities of medium- and long-chain fatty alcohols and lipids against respiratory syncytial virus and parainfluenza virus type 2: comparison at different pH levels.

    Science.gov (United States)

    Hilmarsson, H; Traustason, B S; Kristmundsdóttir, T; Thormar, H

    2007-01-01

    Recent studies have shown that some lipids and fatty alcohols have microbicidal activities against a broad variety of pathogens. In this study, virucidal activities of fatty acids, monoglycerides and fatty alcohols were tested against respiratory syncytial virus (RSV) and human parainfluenza virus type 2 (HPIV2) at different concentrations, times and pH levels. The most active compounds were mixed with milk products and fruit juices and the mixtures tested for virucidal effects. The aim was to determine which compounds are the most active against these respiratory viruses and could possibly be used in pharmaceutical formulations or as additives to milk products or juice. Several compounds caused a significant inactivation of virus, and there was generally a good agreement between the activities against RSV and parainfluenza virus. By changing the pH from 7 to 4.2, the virucidal activities of some of the compounds were greatly increased, i.e., they inactivated virus in a shorter time and at lower concentrations. The most active compound tested was 1-monoglyceride of capric acid, monocaprin, which also showed activity against influenza A virus and significant virucidal activities after addition to milk products and fruit juices, even at a concentration as low as 0.06-0.12%. The significant virucidal activities of fatty alcohols and lipids on RSV and parainfluenza virus demonstrated in this in vitro study raise the question of the feasibility of using such compounds as ingredients in pharmaceutical dosage forms against respiratory infections caused by these viruses, and possibly other paramyxo- and myxoviruses.

  10. Respiratory Syncytial Virus Infections in Infants: Detel1ninants of Clinical Severity

    NARCIS (Netherlands)

    A.H. Brandenburg (Afke)

    2000-01-01

    textabstractIn 1955 a virus was isolated by Morris et al. from a chimpanzee with an upper respiratory tract infection. This apparently new virus was originally called chimpanzee coryza agent. Soon aftclwards, when it was isolated from children with respiratory disease, it became clear that this

  11. Evaluation of a multiplex immunoassay for bovine respiratory syncytial virus and bovine coronavirus antibodies in bulk tank milk against two indirect ELISAs using latent class analysis

    DEFF Research Database (Denmark)

    Toftaker, Ingrid; Toft, Nils; Stokstad, Maria

    2018-01-01

    Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCV) are responsible for respiratory disease and diarrhea in cattle worldwide. The Norwegian control program against these infections is based on herd-level diagnosis using a new multiplex immunoassay. The objective of this study...... was to estimate sensitivity and specificity across different cut-off values for the MVD-Enferplex BCV/BRSV multiplex, by comparing them to a commercially available ELISA, the SVANOVIR® BCV-Ab and SVANOVIR® BRSV-Ab, respectively. We analyzed bulk tank milk samples from 360 herds in a low- and 360 herds in a high...

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

    Science.gov (United States)

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

    2018-03-01

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

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

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

    2016-08-02

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

  14. Characterization of the CD8+ T cell responses directed against respiratory syncytial virus during primary and secondary infection in C57BL/6 mice

    International Nuclear Information System (INIS)

    Lukens, Michael V.; Claassen, Erwin A.W.; Graaff, Patricia M.A. de; Dijk, Mariska E.A. van; Hoogerhout, Peter; Toebes, Mireille; Schumacher, Ton N.; Most, Robbert G. van der; Kimpen, Jan L.L.; Bleek, Grada M. van

    2006-01-01

    The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4 + and CD8 + T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse strains and allow dissection of immune mechanisms by using transgenic and knockout mice that are mostly available on a C57BL/6 background, we characterized the specificity, level and functional capabilities of CD8 + T cells during primary and secondary responses in lung parenchyma, airways and spleens of C57BL/6 mice. During the primary response, epitopes were recognized originating from the matrix, fusion, nucleo- and attachment proteins, whereas the secondary response focused predominantly on the matrix epitope. C57BL/6 mice are less permissive for hRSV infection than BALB/c mice, yet we found CD8 + T cell responses in the lungs and bronchoalveolar lavage, comparable to the responses described for BALB/c mice

  15. Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and SOCS3 in the Different Manner from Endogenous IFN Signaling

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    Junwen Zheng

    2015-01-01

    Full Text Available Respiratory syncytial virus (RSV infection upregulates genes of the suppressor of cytokine signaling (SOCS family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS protein expression plasmids (pNS1, pNS2, and pNS1/2 and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN- α signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-α and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN-α-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling.

  16. Evidence that the respiratory syncytial virus polymerase complex associates with lipid rafts in virus-infected cells: a proteomic analysis

    International Nuclear Information System (INIS)

    McDonald, Terence P.; Pitt, Andrew R.; Brown, Gaie; Rixon, Helen W. McL.; Sugrue, Richard J.

    2004-01-01

    The interaction between the respiratory syncytial virus (RSV) polymerase complex and lipid rafts was examined in HEp2 cells. Lipid-raft membranes were prepared from virus-infected cells and their protein content was analysed by Western blotting and mass spectrometry. This analysis revealed the presence of the N, P, L, M2-1 and M proteins. However, these proteins appeared to differ from one another in their association with these structures, with the M2-1 protein showing a greater partitioning into raft membranes compared to that of the N, P or M proteins. Determination of the polymerase activity profile of the gradient fractions revealed that 95% of the detectable viral enzyme activity was associated with lipid-raft membranes. Furthermore, analysis of virus-infected cells by confocal microscopy suggested an association between these proteins and the raft-lipid, GM1. Together, these results provide evidence that the RSV polymerase complex is able to associate with lipid rafts in virus-infected cells

  17. A Preliminary Assessment of the Role of Ambient Nitric Oxide Exposure in Hospitalization with Respiratory Syncytial Virus Bronchiolitis

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    Nuredin I. Mohammed

    2016-06-01

    Full Text Available Some in vitro studies have indicated a possible link between respiratory syncytial virus (RSV infection and exposure to Nitric Oxide (NO. However, these studies used much higher NO concentrations than normally found in the ambient environment. This preliminary study explored whether an association was present with short-term exposure to NO in the environment. RSV-related admission data between November 2011 and February 2012 were obtained from Sheffield Children’s Hospital. The dates of admission were linked to contemporaneous ambient NO derived from sentinel air monitors. The case-crossover design was used to study the relationship between daily RSV admissions and NO, controlling for temperature and relative humidity. We found little evidence of association between daily RSV admission rates and exposure to ambient NO at different lags or average exposure across several lags. The findings should, however, be viewed with caution due to the low number of events observed during the time frame. It is possible that the apparent lack of association may be accounted for by the timing of the seasonal RSV epidemic in relation to peaks in NO concentrations. A larger study incorporating a wider range of RSV and NO peaks would determine whether said peaks enhanced the number of RSV hospitalizations in children.

  18. Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus.

    Science.gov (United States)

    McLellan, Jason S; Correia, Bruno E; Chen, Man; Yang, Yongping; Graham, Barney S; Schief, William R; Kwong, Peter D

    2011-06-24

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 Å resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required. Published by Elsevier Ltd.

  19. Analysis of biennial outbreak pattern of respiratory syncytial virus according to subtype (A and B) in the Zagreb region.

    Science.gov (United States)

    Mlinaric-Galinovic, Gordana; Tabain, Irena; Kukovec, Tamara; Vojnovic, Gordana; Bozikov, Jadranka; Bogovic-Cepin, Jasna; Ivkovic-Jurekovic, Irena; Knezovic, Ivica; Tesovic, Goran; Welliver, Robert C

    2012-06-01

    The epidemic pattern of respiratory syncytial virus (RSV) in Croatia is biennial. In order to determine if the circulation of different RSV subtypes affects the outbreak cycle, the aim of the present study was to analyze the epidemic pattern of RSV in children in Croatia (Zagreb region) over a period of 3 consecutive years. The study group consisted of 696 inpatients, aged 0-5 years, who were hospitalized with acute respiratory tract infections caused by RSV, in Zagreb, in the period 1 January 2006-31 December 2008. The virus was identified in nasopharyngeal secretions using direct immunofluorescence. The virus subtype was determined on real-time polymerase chain reaction. Of 696 RSV infections identified in children, subtype A virus caused 374 infections, and subtype B, 318. Four patients had a dual RSV infection (subtypes A and B). The period of study was characterized by four epidemic waves of RSV infections: the first, smaller, in the spring of 2006; the second, larger, in December 2006/January 2007; the third in spring 2008, followed by a fourth outbreak beginning in November of 2008. The biennial virus cycles were persistent although the predominant RSV subtype in the first two epidemic waves was subtype B, and in the second two it was subtype A. Over a 3 year period of observation, the biennial RSV cycle in Croatia cannot be explained by a difference in the predominant circulating subtype of RSV. Other unknown factors account for the biennial cycle of RSV epidemics in Croatia. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

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

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    Maarten O Blanken

    Full Text Available 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.The RISK study consisted of 2 multicenter prospective birth cohorts in 41 hospitals. Risk factors were assessed at birth among healthy preterm infants 33-35 WGA. All hospitalizations for respiratory tract infection were screened for proven RSV infection by immunofluorescence or polymerase chain reaction. Multivariate logistic regression analysis was used to update an existing prediction model in the derivation cohort (n = 1,227. In the validation cohort (n = 1,194, predicted versus actual RSV hospitalization rates were compared to determine validity of the model.RSV hospitalization risk in both cohorts was comparable (5.7% versus 4.9%. In the derivation cohort, a prediction rule to determine probability of RSV hospitalization was developed using 4 predictors: family atopy (OR 1.9; 95%CI, 1.1-3.2, birth period (OR 2.6; 1.6-4.2, breastfeeding (OR 1.7; 1.0-2.7 and siblings or daycare attendance (OR 4.7; 1.7-13.1. The model showed good discrimination (c-statistic 0.703; 0.64-0.76, 0.702 after bootstrapping. External validation showed good discrimination and calibration (c-statistic 0.678; 0.61-0.74.Our prospectively validated prediction rule identifies infants at increased RSV hospitalization risk, who may benefit from targeted preventive interventions. This prediction rule can facilitate country-specific, cost-effective use of RSV prophylaxis in late preterm infants.

  1. Age related changes in T cell mediated immune response and effector memory to Respiratory Syncytial Virus (RSV in healthy subjects

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    Campoccia Giuseppe

    2010-10-01

    Full Text Available Abstract Respiratory syncytial virus (RSV is the major pathogen causing respiratory disease in young infants and it is an important cause of serious illness in the elderly since the infection provides limited immune protection against reinfection. In order to explain this phenomenon, we investigated whether healthy adults of different age (20-40; 41-60 and > 60 years, have differences in central and effector memory, RSV-specific CD8+ T cell memory immune response and regulatory T cell expression status. In the peripheral blood of these donors, we were unable to detect any age related difference in term of central (CD45RA-CCR7+ and effector (CD45RA-CCR7- memory T cell frequency. On the contrary, we found a significant increase in immunosuppressive regulatory (CD4+25+FoxP3+ T cells (Treg in the elderly. An immunocytofluorimetric RSV pentamer analysis performed on these donors' peripheral blood mononuclear cells (PBMCs, in vitro sensitized against RSV antigen, revealed a marked decline in long-lasting RSV specific CD8+ memory T cell precursors expressing interleukin 7 receptor α (IL-7Rα, in the elderly. This effect was paralleled by a progressive switch from a Th1 (IFN-γ and TNF-α to a Th2 (IL-10 functional phenotype. On the contrary, an increase in Treg was observed with aging. The finding of Treg over-expression status, a prominent Th2 response and an inefficient RSV-specific effector memory CD8+ T cell expansion in older donors could explain the poor protection against RSV reinfection and the increased risk to develop an RSV-related severe illness in this population. Our finding also lays the basis for new therapeutic perspectives that could limit or prevent severe RSV infection in elderly.

  2. Vaccine Induced Herd Immunity for Control of Respiratory Syncytial Virus Disease in a Low-Income Country Setting.

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    Timothy M Kinyanjui

    Full Text Available Respiratory syncytial virus (RSV is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently RSV is the most important viral cause of respiratory morbidity and mortality in young children. Development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems. Vaccine development for young infants has been unsuccessful, but this is not the case for older children (> 6 m. Would vaccinating older children have a significant public health impact? We developed a mathematical model to explore the benefits of a vaccine against RSV.We have used a deterministic age structured model capturing the key epidemiological characteristics of RSV and performed a statistical maximum-likelihood fit to age-specific hospitalization data from a developing country setting. To explore the effects of vaccination under different mixing assumptions, we included two versions of contact matrices: one from a social contact diary study, and the second a synthesised construction based on demographic data. Vaccination is assumed to elicit an immune response equivalent to primary infection. Our results show that immunisation of young children (5-10 m is likely to be a highly effective method of protection of infants (<6 m against hospitalisation. The majority benefit is derived from indirect protection (herd immunity. A full sensitivity and uncertainty analysis using Latin Hypercube Sampling of the parameter space shows that our results are robust to model structure and model parameters.This result suggests that vaccinating older infants and children against RSV can have a major public health benefit.

  3. Respiratory syncytial virus (RSV bronchiolitis: comparative study of RSV groups A and B infected children

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    Selir M. Straliotto

    1994-03-01

    Full Text Available The grouping characteristics of 29 respiratory syncitial virus (RSV present in nasopharyngeal cells collectedfrom hospitalized children with bronchiolitis during the 1990RSVseason in Porto Alegre, RS, were analysed. Twenty-two were grouped as belonging to group A and 7 to group B. Cyanosis, oxigen therapy, cough, lenght of hospitalization and atelectasis were observed to be more frequently found within group B infected children. Other clinical signs and symptoms were similarly found in both groups.

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

    Science.gov (United States)

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

    2017-04-01

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

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

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    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.

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

    Science.gov (United States)

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

    2011-06-01

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

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

    Science.gov (United States)

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

    2017-07-26

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

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

    Science.gov (United States)

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

    2017-08-14

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

  9. [INF-gamma during respiratory-syncytial induced obstructive respiratory syndrome in infection in children under one year of age].

    Science.gov (United States)

    Kandelaki, E T; Nemsadze, K P; Chkhaidze, I G; Kherkheulidze, M N; Kamkamidze, G K

    2005-12-01

    Lately the connection of Asthma and RSV drew the sufficient attention. The recurrent wheezing developed during the RSV in children is particularly frequent in the families having history of atopy. The decreased expression of INFgamma may play the role in the pathogenesis of RSV infection. The target of our research was the study of the rate of INFgamma during various clinical courses of RSV-infection and definition of its role in the pathogenesis of ARVI. 52 children with RSV-associated wheezing have been studied, who had first (32) or recurrent episode (20) of bronchial obstruction and whose families had occurrence of atopy. 52 children with non RSV-associated wheezing (III group) and 10 healthy children up to 12 months of age (IV group) were considered as the control groups. Children from all four groups were from families with the history of atopy. INFgamma was measured by enzyme immunoassay (ELISA). Comparison of two groups of wheezing children with RSV infection showed significant reduction of INFgamma level in the group of children with recurrent wheezing vs. the group with first episode of wheezing. INFgamma levels were significantly higher in the two control groups. During the acute respiratory infection induced by RS-virus, which proceeds with the obstruction of respiratory tract (wheezing), reduction of INFgamma was noted and higher frequency of wheezing episodes is associated with more prominent alteration.

  10. Structural analysis of respiratory syncytial virus reveals the position of M2-1 between the matrix protein and the ribonucleoprotein complex.

    Science.gov (United States)

    Kiss, Gabriella; Holl, Jens M; Williams, Grant M; Alonas, Eric; Vanover, Daryll; Lifland, Aaron W; Gudheti, Manasa; Guerrero-Ferreira, Ricardo C; Nair, Vinod; Yi, Hong; Graham, Barney S; Santangelo, Philip J; Wright, Elizabeth R

    2014-07-01

    Respiratory syncytial virus (RSV), a member of the Paramyxoviridae family of nonsegmented, negative-sense, single-stranded RNA genome viruses, is a leading cause of lower respiratory tract infections in infants, young children, and the elderly or immunocompromised. There are many open questions regarding the processes that regulate human RSV (hRSV) assembly and budding. Here, using cryo-electron tomography, we identified virus particles that were spherical, filamentous, and asymmetric in structure, all within the same virus preparation. The three particle morphologies maintained a similar organization of the surface glycoproteins, matrix protein (M), M2-1, and the ribonucleoprotein (RNP). RNP filaments were traced in three dimensions (3D), and their total length was calculated. The measurements revealed the inclusion of multiple full-length genome copies per particle. RNP was associated with the membrane whenever the M layer was present. The amount of M coverage ranged from 24% to 86% in the different morphologies. Using fluorescence light microscopy (fLM), direct stochastic optical reconstruction microscopy (dSTORM), and a proximity ligation assay (PLA), we provide evidence illustrating that M2-1 is located between RNP and M in isolated viral particles. In addition, regular spacing of the M2-1 densities was resolved when hRSV viruses were imaged using Zernike phase contrast (ZPC) cryo-electron tomography. Our studies provide a more complete characterization of the hRSV virion structure and substantiation that M and M2-1 regulate virus organization. hRSV is a leading cause of lower respiratory tract infections in infants and young children as well as elderly or immunocompromised individuals. We used cryo-electron tomography and Zernike phase contrast cryo-electron tomography to visualize populations of purified hRSV in 3D. We observed the three distinct morphologies, spherical, filamentous, and asymmetric, which maintained comparable organizational profiles

  11. Epidemiology of respiratory syncytial virus in children ≤2 years of age hospitalized with lower respiratory tract infections in the Russian Federation: a prospective, multicenter study

    Directory of Open Access Journals (Sweden)

    Vladimir Tatochenko

    2010-09-01

    Full Text Available Vladimir Tatochenko1, Vasily Uchaikin2, Aleksandr Gorelov3, Konstantin Gudkov4, Andrew Campbell5, Gregory Schulz5, Rebecca Prahl5, Gerard Notario51Scientific Centre of Children’s Health, Russian Academy of Medical Sciences, Lomonosovskiy Prospect, Moscow, Russia; 2Russian State Medical University of Roszdrav, Moscow, Russia; 3Central Scientific Research Institution of Epidemiology, Moscow, Russia; 4Abbott Laboratories LLC, Khimki, Moscow, Russia; 5Abbott Laboratories, Abbott Park, IL, USABackground: Respiratory syncytial virus (RSV is the leading cause of severe lower respiratory tract infections among infants and young children, and is responsible for an estimated four million deaths per year globally. A monthly injection of palivizumab has been used for prophylaxis of serious RSV infections among high-risk children in 71 countries since 1998 and approval for use in the Russian Federation was obtained in February 2010. A recommendation for RSV prophylaxis in the Russian Federation would require knowledge of the prevalence and seasonality of RSV in that country.Methods: In a prospective, multicenter, epidemiological study of the prevalence, seasonality, and peak occurrence of RSV infection, children aged ≤2 years hospitalized for lower respiratory tract infections in three regions of the Russian Federation, from September 2008 through April 2009, were screened and tested for RSV using rapid immunochromatography of nasopharyngeal lavage. For subjects who were tested positive, hospitalization data were collected.Results: Of 519 children aged ≤2 years enrolled from September 11, 2008 through April 26, 2009, 197 tested positive for RSV (38.0%, 95% CI: 33.8, 42.3. The onset of the 2008–2009 RSV season in the Russian Federation occurred in late October 2008, similar to what is observed in other northern temperate zones. Peak activity occurred in early April 2009, when 62% of children enrolled tested positive for RSV.Conclusion: The prevalence

  12. Respiratory syncytial virus (RSV disease – new data needed to guide future policy

    Directory of Open Access Journals (Sweden)

    Louis Bont

    2015-12-01

    Full Text Available RSV is the main cause of childhood lower respiratory infections, globally, an important cause of childhood wheeze and may be responsible for a substantial burden of disease in the very elderly and in adults with chronic medical problems, such as COPD. It is thus responsible for substantial healthcare and social costs. There are currently many companies and academic groups developing and testing candidate vaccines and there is an expectation that these will lead to effective and safe vaccines which will be available to health systems globally in the short- medium term. Despite this, there is an incomplete understanding of RSV disease, especially in adult groups, and large scale data are only available from a few countries and settings leading to low levels of awareness of the importance of this pathogen. We discuss the need for widespread national sentinel systems of RSV surveillance and some means by which this could be achieved. These data will be needed by national policy makers and immunisation advisory groups to guide future priority setting and decision making.

  13. Respiratory syncytial virus (RSV bronchiolitis: comparative study of RSV groups A and B infected children

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    Selir M. Straliotto

    1994-03-01

    Full Text Available The grouping characteristics of 29 respiratory syncitial virus (RSV present in nasopharyngeal cells collectedfrom hospitalized children with bronchiolitis during the 1990RSVseason in Porto Alegre, RS, were analysed. Twenty-two were grouped as belonging to group A and 7 to group B. Cyanosis, oxigen therapy, cough, lenght of hospitalization and atelectasis were observed to be more frequently found within group B infected children. Other clinical signs and symptoms were similarly found in both groups.Estudos recentes de amostras do vírus respiratório sincicial (VRS usando anticorpos monoclonais distiguiram duas variantes antigênicas, designadas como grupos A e B. Estes grupos foram estudados em 29 secreções de nasofaringe positivas para o VRS, provenientes de crianças hospitalizadas com bronquiolite durante surto de virose por VRS, em Porto Alegre, em 1990. Destas, 22 foram grupadas como pertencentes ao grupo A e 7 ao grupo B. Alguns achados clínicos como cianose, tosse, uso de oxigênio e dias de hospitalização foram mais freqüentemente observados em crianças infectadas coin o grupo B do VRS. Outros sinais e sintomas clínicos foram similarmente encontrados nos 2 grupos.

  14. ROLE OF PREEXISTING VIRUS-SPECIFIC IgG IN PRIMARY DISEASE AND IN REINFECTION WITH RESPIRATORY SYNCYTIAL VIRUS

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    V. Z. Krivitskaya

    2012-01-01

    Full Text Available Abstract. The aim of the study is evaluation of links between presence in blood of specific pre-existing IgG to respiratory-syncytial virus (RSV, clinical course of RSV infection and character specific to RSV humoral immune response in patients of different ages. The antibodies were detected by ELISA using whole RS virus or synthetic peptides corresponded to the selected determinants of the envelope RSV proteins. It was shown that RS specific maternal IgG antibodies passively transferred to babies in utero can circulate in the blood up to 10 months of life. The analysis of paired sera of 45 babies in the age of 1–10 months revealed firstly that presence of maternal IgG specific antibodies to the conservative B-cell immunogenic determinants of the F-protein (amino acids 221–232 and/or the G-protein (amino acids 152–164 and 184–198 is coupled with more high morbidity of primary RSV infection (89% versus 56%, p = 0.023, and also with more high frequency of complicated by bronchus obstruction course of the disease (81% versus 20%, р = 0.001 in compare with babies who were serologically negative to the maternal determinants specific antibodies. The correlation analysis has shown that the high presence of maternal determinant-specific IgG in the blood in babies till 10 months of life is associated in the case of primary infection with disbalance of humoral anti-viral immune response: intensive synthesis of serum RSV IgA. This is evidence of complicated course of infection with simultaneous suppression of response to RSV specific IgG. As opposed to the primary RSV infection in patients older than 3 years (n = 121 it was not detected links between anamnestic determinant-specific IgG synthesized by own immune system as the results of previous disease episodes and synthesis of anti-RSV IgG, IgM, IgE and IgA in RSV re-infections. In the contrast to babies in more older patients the feedback connection between level of pre-existing determinant

  15. Bovine respiratory syncytial virus and bovine coronavirus antibodies in bulk tank milk - risk factors and spatial analysis.

    Science.gov (United States)

    Toftaker, Ingrid; Sanchez, Javier; Stokstad, Maria; Nødtvedt, Ane

    2016-10-01

    Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCoV) are considered widespread among cattle in Norway and worldwide. This cross-sectional study was conducted based on antibody-ELISA of bulk tank milk (BTM) from 1347 herds in two neighboring counties in western Norway. The study aims were to determine the seroprevalence at herd level, to evaluate risk factors for BRSV and BCoV seropositivity, and to assess how these factors were associated with the spatial distribution of positive herds. The overall prevalence of BRSV and BCoV positive herds in the region was 46.2% and 72.2%, respectively. Isopleth maps of the prevalence risk distribution showed large differences in prevalence risk across the study area, with the highest prevalence in the northern region. Common risk factors of importance for both viruses were herd size, geographic location, and proximity to neighbors. Seropositivity for one virus was associated with increased odds of seropositivity for the other virus. Purchase of livestock was an additional risk factor for BCoV seropositivity, included in the model as in-degree, which was defined as the number of incoming movements from individual herds, through animal purchase, over a period of five years. Local dependence and the contribution of risk factors to this effect were assessed using the residuals from two logistic regression models for each virus. One model contained only the x- and y- coordinates as predictors, the other had all significant predictors included. Spatial clusters of high values of residuals were detected using the normal model of the spatial scan statistic and visualized on maps. Adjusting for the risk factors in the final models had different impact on the spatial clusters for the two viruses: For BRSV the number of clusters was reduced from six to four, for BCoV the number of clusters remained the same, however the log-likelihood ratios changed notably. This indicates that geographical differences in proximity to

  16. Association of Age With Risk of Hospitalization for Respiratory Syncytial Virus in Preterm Infants With Chronic Lung Disease.

    Science.gov (United States)

    Winterstein, Almut G; Choi, Yoonyoung; Meissner, H Cody

    2018-02-01

    It is unknown whether the age threshold (≤24 months) for preterm infants with chronic lung disease (CLD) to receive immunoprophylaxis for respiratory syncytial virus (RSV) as currently recommended by American Academy of Pediatrics guidelines correctly identified infants at higher risk for hospitalization for RSV. To determine the age when the risk of hospitalization for RSV among preterm infants with CLD becomes equivalent to the risk for healthy, 1-month-old term infants who do not qualify for immunoprophylaxis. A retrospective cohort study was conducted of 1 018 593 healthy term infants and 5181 preterm infants with CLD using Medicaid billing records (Medicaid Analytic eXtract files) from January 1, 1999, to December 31, 2010, linked to Florida and Texas birth and death certificates. Age-trend discrete time logistic regression models within a survival analysis framework were developed, adjusting for covariates including the use of immunoprophylaxis, to compare the risk of hospitalization of preterm infants (CLD at 3 through 34 months of age with the risk of hospitalization of term infants (37-41 weeks' gestational age) at 1 month of age. Age at which risk of hospitalization for RSV among preterm infants with CLD equals the risk for healthy term infants at age 1 month. The study cohort included 1 018 593 healthy term infants and 5181 preterm infants with CLD; because patients could reenter the cohort for a second or third season, the total study cohort consisted of 1 880 531 healthy term infant-seasons (926 206 girls and 954 325 boys; mean [SD] age at first season entry, 12.6 [9.6] months) and 8680 CLD infant-seasons (3519 girls and 5161 boys; mean [SD] age at first season entry, 15.1 [9.1] months). Among term infants with siblings, the risk of hospitalization for RSV averaged across all covariate strata was 9.0 (95% CI, 8.4-9.6) per 1000 patient season-months at 1 month of age. The risk of hospitalization for RSV among preterm infants with CLD

  17. Costs of hospitalization with respiratory syncytial virus illness among children aged <5 years and the financial impact on households in Bangladesh, 2010.

    Science.gov (United States)

    Bhuiyan, Mejbah Uddin; Luby, Stephen P; Alamgir, Nadia Ishrat; Homaira, Nusrat; Sturm-Ramirez, Katharine; Gurley, Emily S; Abedin, Jaynal; Zaman, Rashid Uz; Alamgir, Asm; Rahman, Mahmudur; Ortega-Sanchez, Ismael R; Azziz-Baumgartner, Eduardo

    2017-06-01

    Respiratory syncytial virus (RSV) is the leading cause of acute respiratory illness in young children and results in significant economic burden. There is no vaccine to prevent RSV illness but a number of vaccines are in development. We conducted this study to estimate the costs of severe RSV illness requiring hospitalization among children 50% families borrowed money to meet treatment cost. We estimated that the median direct cost of RSV-associated hospitalization in children aged <5 years in Bangladesh was US$ 10 million (IQR: US$ 7-16 million), the median indirect cost was US$ 3.0 million (IQR: 2-5 million) in 2010. RSV-associated hospitalization among children aged <5 years represents a substantial economic burden in Bangladesh. Affected families frequently incurred considerable out of pocket and indirect costs for treatment that resulted in financial hardship.

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

    Science.gov (United States)

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

    2014-01-01

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

  19. Respiratory Syncytial Virus Infection as a Precipitant of Thyroid Storm in a Previously Undiagnosed Case of Graves' Disease in a Prepubertal Girl

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    Charlton RWilliam

    2011-03-01

    Full Text Available Graves' disease is less common in prepubertal than pubertal children, and initial presentation with thyroid storm is rare. We report an 11-year-old prepubertal Hispanic girl who presented with a one-day history of respiratory distress, fever, and dysphagia. She had exophthalmos, a diffuse bilateral goiter and was agitated, tachycardic, and hypertensive. Nasal swab was positive for respiratory syncytial virus (RSV. She was diagnosed with thyroid storm and admitted to the pediatric intensive care unit. While infection is a known precipitant of thyroid storm and RSV is a common pediatric infection, to the best of our knowledge, this is the first reported case of RSV infection apparently precipitating thyroid storm in a prepubertal child.

  20. 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......, in addition, 10 animals that were negative with the ELISA were positive with the RT-PCR assay. These results indicates that the RT-PCR assay can be a sensitive, reliable alternative to conventional diagnostic procedures....... 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...

  1. Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta–analysis

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    Ting Shi

    2015-12-01

    Full Text Available Respiratory syncytial virus (RSV is the most common pathogen identified in young children with acute lower respiratory infection (ALRI as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV–associated ALRI. We aimed to identify risk factors for RSV–associated ALRI in young children. We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta–analyses to estimate odds ratios with 95% confidence intervals (CI for individual risk factors. We identified 20 studies (3 were unpublished data with “good quality” that investigated 18 risk factors for RSV–associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV–associated ALRI. The meta–estimates of their odds ratio (ORs with corresponding 95% confidence intervals (CI are prematurity 1.96 (95% CI 1.44–2.67, low birth weight 1.91 (95% CI 1.45–2.53, being male 1.23 (95% CI 1.13–1.33, having siblings 1.60 (95% CI 1.32–1.95, maternal smoking 1.36 (95% CI 1.24–1.50, history of atopy 1.47 (95% CI 1.16–1.87, no breastfeeding 2.24 (95% CI 1.56–3.20 and crowding 1.94 (95% CI 1.29–2.93. Although there were insufficient studies available to generate a meta–estimate for HIV, all articles (irrespective of quality scores reported significant associations between HIV and RSV–associated ALRI. This study presents a comprehensive report of the strength of association between various socio–demographic risk factors and RSV–associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause ALRI and

  2. The burden of respiratory syncytial virus (RSV) associated acute lower respiratory infections in children with Down syndrome: A systematic review and meta-analysis.

    Science.gov (United States)

    Chan, Markus; Park, John J; Shi, Ting; Martinón-Torres, Federico; Bont, Louis; Nair, Harish

    2017-12-01

    Acute lower respiratory tract infections (ALRIs) caused by respiratory syncytial virus (RSV) are a leading cause of hospitalization in infants. Numerous risk factors have been identified in the aetiology of severe RSV-associated ALRI necessitating hospitalisation, including prematurity and congenital heart disease. Down syndrome (DS), a common genetic disorder associated with congenital and dysmorphic features, has recently been identified as an independent risk factor for RSV-associated ALRI requiring hospitalisation; however, the disease burden of RSV-associated ALRI in this population has not yet been established. Similarly, the impact of DS as an independent risk factor has not yet been quantified. We aimed therefore to estimate the incidence of admissions in children with DS, and by comparing this with unaffected children, to quantify the risk of DS independent of other risk factors. A systematic review of the existing literature published between 1995 and March 1, 2017 was performed to quantify the incidence of hospitalisation due to RSV-associated ALRI in children with DS. Meta-analyses were performed on extracted data using STATA statistical software, and hospitalisation rates for children with and without DS under the age of 2 were calculated. 5 articles were ultimately deemed eligible for analyses. Analyses were limited to children under the age of 2 years. We calculated the hospitalisation rate for children with DS in this age group to be 117.6 per 1000 child-years (95% CI 67.4-205.2), vs a rate of 15.2 per 1000 child-years (95% CI 8.3-27.6) in unaffected children. This indicates DS contributes to a 6.8 (95% CI 5.5-8.4) fold increase in the relative risk of hospitalisation for RSV-associated ALRI. Though limited by a small number of articles, this review found sufficient evidence to conclude DS was a significant independent risk factor for the development of severe RSV-associated ALRI requiring hospitalisation. Further studies are needed to define the

  3. Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV): consequences of deficient interferon-dependent antiviral defense

    International Nuclear Information System (INIS)

    Echchgadda, Ibtissam; Chang, Te-Hung; Sabbah, Ahmed; Bakri, Imad; Ikeno, Yuji; Hubbard, Gene B; Chatterjee, Bandana; Bose, Santanu

    2011-01-01

    Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human respiratory syncytial virus (RSV) is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells. The present study extends the result to androgen-dependent prostate cancer, and explores the underlying mechanism that triggers RSV-induced oncolysis of prostate cancer cells. The oncolytic effect of RSV on androgen-sensitive LNCaP human prostate cancer cells and on androgen-independent RM1 murine prostate cancer cells was studied in vitro in culture and in vivo in a xenograft or allograft tumor model. In vitro, cell viability, infectivity and apoptosis were monitored by MTT assay, viral plaque assay and annexin V staining, respectively. In vivo studies involved virus administration to prostate tumors grown in immune compromised nude mice and in syngeneic immune competent C57BL/6J mice. Anti-tumorogenic oncolytic activity was monitored by measuring tumor volume, imaging bioluminescent tumors in live animals and performing histopathological analysis and TUNEL assay with tumors We show that RSV imposes a potent oncolytic effect on LNCaP prostate cancer cells. RSV infectivity was markedly higher in LNCaP cells compared to the non-tumorigenic RWPE-1 human prostate cells. The enhanced viral burden led to LNCaP cell apoptosis and growth inhibition of LNCaP xenograft tumors in nude mice. A functional host immune response did not interfere with RSV-induced oncolysis, since growth of xenograft tumors in syngeneic C57BL/6J mice from murine RM1 cells was inhibited upon RSV administration. LNCaP cells failed to activate the type-I interferon (IFNα/β)-induced transcription factor STAT-1, which is required for antiviral gene expression, although these cells could produce IFN in response to RSV infection. The essential role of IFN in restricting infection was further

  4. Respiratory Syncytial Virus (RSV)

    Science.gov (United States)

    ... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

  5. 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

    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...... was found to correlate well with the severity of clinical signs (fever) and with the extent of lung consolidation while SAA responded most rapidly to infection....

  6. Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS triggered by respiratory syncytial virus (RSV infection: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Jun Makino

    2017-01-01

    Full Text Available We present a unique and informative instance of respiratory syncytial virus (RSV infection associated with antiphospholipid syndrome (APS, and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.

  7. Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature.

    Science.gov (United States)

    Makino, Jun; Koshy, Sanjana; Bajaj, Sonal; Jeong, Young-Gwang; Perlman, David C

    2017-01-01

    We present a unique and informative instance of respiratory syncytial virus (RSV) infection associated with antiphospholipid syndrome (APS), and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.

  8. Absence of Association between Cord Specific Antibody Levels and Severe Respiratory Syncytial Virus (RSV) Disease in Early Infants: A Case Control Study from Coastal Kenya.

    Science.gov (United States)

    Nyiro, Joyce Uchi; Sande, Charles Jumba; Mutunga, Martin; Kiyuka, Patience Kerubo; Munywoki, Patrick Kioo; Scott, John Anthony G; Nokes, David James

    2016-01-01

    The target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development. A case control study nested in a birth cohort (2002-07) was conducted in Kilifi, Kenya; where 30 hospitalised cases of RSV-associated severe disease were matched to 60 controls. Participants had a cord blood and 2 subsequent 3-monthly blood samples assayed for RSV-specific neutralising antibody by the plaque reduction neutralisation test (PRNT). Two sample paired t test and conditional logistic regression were used in analyses of log2PRNT titres. The mean RSV log2PRNT titre at birth for cases and controls were not significantly different (P = 0.4) and remained so on age-stratification. Cord blood PRNT titres showed considerable overlap between cases and controls. The odds of RSV disease decreased with increase in log2PRNT cord blood titre. There was a 30% reduction in RSV disease per unit increase in log2PRNT titre (disease. Cord antibody levels show wide variation with considerable overlap between cases and controls. It is likely that, there are additional factors to specific PRNT antibody levels which determine susceptibility to severe RSV disease. In addition, higher levels of neutralizing antibody beyond the normal range may be required for protection; which it is hoped can be achieved by a maternal RSV vaccine.

  9. Up-regulation of serum periostin and squamous cell carcinoma antigen levels in infants with acute bronchitis due to respiratory syncytial virus

    Directory of Open Access Journals (Sweden)

    Hiroaki Nakamura

    2018-04-01

    Full Text Available Background: Periostin and squamous cell carcinoma antigen (SCCA are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated. Methods: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI had been met: Group I consisted of mAPI (+ and mAPI (− patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339. Results: We enrolled 14 subjects in Group I mAPI (+, 22 in Group I mAPI (−, 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+ and mAPI (−. Conclusions: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV. Keywords: Infants, Periostin, Respiratory syncytial virus, Squamous cell carcinoma antigen, T-helper 2 cell cytokines

  10. A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease.

    Science.gov (United States)

    Wiegand, Marian Alexander; Gori-Savellini, Gianni; Gandolfo, Claudia; Papa, Guido; Kaufmann, Christine; Felder, Eva; Ginori, Alessandro; Disanto, Maria Giulia; Spina, Donatella; Cusi, Maria Grazia

    2017-05-15

    Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component. In this way, the antigen is actively expressed on the surfaces of vaccine particles in its prefusion conformation, and as recently reported for other vectored vaccines, the occurrence of silencing mutations of the transgene in the vaccine genome can be prevented. In addition, its active gene expression contributes to further stimulation of the immune response. In order to understand the best route of immunization, we compared vaccine efficacies after intranasal (i.n.) or intramuscular (i.m.) immunization of BALB/c mice. Via both routes, substantial RSV-specific immune responses were induced, consisting of serum IgG and neutralizing antibodies, as well as cytotoxic T cells. Moreover, i.n. immunization was also able to stimulate specific mucosal IgA in the upper and lower respiratory tract. In virus challenge experiments, animals were protected against RSV infection after both i.n. and i.m. immunization without inducing vaccine-enhanced disease. Above all, the replication-deficient SeV appeared to be safe and well tolerated. IMPORTANCE Respiratory syncytial virus (RSV) is a major cause of respiratory diseases in young children and elderly people worldwide. There is a great demand for a licensed vaccine. Promising existing vaccine approaches based on live-attenuated vaccines or viral vectors have suffered from unforeseen drawbacks related to immunogenicity

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

    Science.gov (United States)

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

    2015-12-01

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

  12. The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection.

    Science.gov (United States)

    Bakre, Abhijeet A; Harcourt, Jennifer L; Haynes, Lia M; Anderson, Larry J; Tripp, Ralph A

    2017-07-03

    Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182-186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting.

  13. Discovery of a Prefusion Respiratory Syncytial Virus F-Specific Monoclonal Antibody That Provides Greater In Vivo Protection than the Murine Precursor of Palivizumab.

    Science.gov (United States)

    Zhao, Min; Zheng, Zi-Zheng; Chen, Man; Modjarrad, Kayvon; Zhang, Wei; Zhan, Lu-Ting; Cao, Jian-Li; Sun, Yong-Peng; McLellan, Jason S; Graham, Barney S; Xia, Ning-Shao

    2017-08-01

    Palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations of the respiratory syncytial virus (RSV) F glycoprotein, is the only prophylactic agent approved for use for the treatment of RSV infection. However, its relatively low neutralizing potency and high cost have limited its use to a restricted population of infants at high risk of severe disease. Previously, we isolated a high-potency neutralizing antibody, 5C4, that specifically recognizes antigenic site Ø at the apex of the pre-F protein trimer. We compared in vitro and in vivo the potency and protective efficacy of 5C4 and the murine precursor of palivizumab, antibody 1129. Both antibodies were synthesized on identical murine backbones as either an IgG1 or IgG2a subclass and evaluated for binding to multiple F protein conformations, in vitro inhibition of RSV infection and propagation, and protective efficacy in mice. Although 1129 and 5C4 had similar pre-F protein binding affinities, the 5C4 neutralizing activity was nearly 50-fold greater than that of 1129 in vitro In BALB/c mice, 5C4 reduced the peak titers of RSV 1,000-fold more than 1129 did in both the upper and lower respiratory tracts. These data indicate that antibodies specific for antigenic site Ø are more efficacious at preventing RSV infection than antibodies specific for antigenic site II. Our data also suggest that site Ø-specific antibodies may be useful for the prevention or treatment of RSV infection and support the use of the pre-F protein as a vaccine antigen. IMPORTANCE There is no vaccine yet available to prevent RSV infection. The use of the licensed antibody palivizumab, which recognizes site II on both the pre-F and post-F proteins, is restricted to prophylaxis in neonates at high risk of severe RSV disease. Recommendations for using passive immunization in the general population or for therapy in immunocompromised persons with

  14. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  15. Molecular characterization of circulating respiratory syncytial virus (RSV genotypes in Gilgit Baltistan Province of Pakistan during 2011-2012 winter season.

    Directory of Open Access Journals (Sweden)

    Uzma Bashir

    Full Text Available Respiratory syncytial virus (RSV is the major cause of acute lower respiratory tract infections in young children, but very little is known about its epidemiology and circulating genotypes in Pakistan. This study analyzed the epidemiological and molecular characteristics of RSV genotypes detected in Pakistani children less than 2 years of age with acute respiratory tract infections (ARIs in a tertiary care hospital in Gilgit Baltistan (GB province during 2011-12 winter season. RSV was detected in 75 out of 105 children presenting with acute respiratory infection. Male infants between 2-6 months age made up the highest percentage of RSV positive cases. Epidemiological factors such as pre-maturity, mean weight, clinical features and diagnosis when compared between RSV positive and negative groups were found to be statistically insignificant. Phylogenetic analysis classified all 75 of the RSV strains into 71 strains of subgroups A and 4 strains of subgroup B, respectively. Strains belonging to subgroups A and B were further subdivided into NA1/GA2 and BA, respectively. The nucleotide and deduced amino acid sequence identities were relatively high among these strains (>90%. Both RSV-A and RSV-B isolates had two potential N-glycosylation sites in HVR2 of G protein and with heavy O-glycosylation of serine and threonine residues (G scores of 0.5-0.7. This report highlights the significance of RSV as a dominant viral etiologic agent of pediatric ARIs, and need for continued molecular epidemiological surveys for early detection of prevalent strains and newly emerging genotypes to understand epidemiology of RSV infections in various regions of Pakistan.

  16. 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...... phase of infection. A secondary response may be more likely in children with low IgM responses in the acute phase (RR = 2.08 (95% confidence interval (CI) 0.92-4.70)). The IgA response was highest on days 28 and 42 after antigen detection, 72% having a detectable IgA response within the first 1.5 mo...... have therefore assessed the duration of secretory IgM and IgA antibody responses and whether assays for these antibodies can be used to improve the diagnosing of RSV-associated infections. During two RSV epidemics in Guinea-Bissau, 32 RSV antigen-positive children with LRI were followed with sequential...

  17. A cost-benefit analysis of the immunisation of children against respiratory syncytial virus (RSV) using the English Hospital Episode Statistics (HES) data set.

    Science.gov (United States)

    Thomas, Gareth

    2018-03-01

    Respiratory syncytial virus (RSV) is a common cause of respiratory infection that is highly prevalent in infants, particularly those with underlying medical conditions. Severe cases of RSV require hospitalisation as well as admission to intensive care and may even result in death. The objective of the study was to measure the net benefits that could arise from an immunisation programme of infants that may well eradicate RSV to a high degree and save the direct and indirect medical care costs from hospitalisation, morbidity and the gain from potential life-time earnings by reducing the probability of mortality. In this context, the majority of existing empirical investigations are based on data from clinical trials, and where relevant facts are not available, a series of strong assumptions is derived from the published literature, whereas in this study, for the first time, the hospital episode statistics database is used to calculate the cost-benefit ratios. The methodology of the analysis adopts a cost-benefit approach to assess the impact of the immunisation and whether it is beneficial to society. The underlying assumptions of the basic model are assessed by adopting a sensitivity analysis. The results show that a number of categories are cost-effective with the use of the passive drug, which means benefits by raising the life expectancy and quality as well as reducing the resource burden on society.

  18. Nation-wide surveillance of human acute respiratory virus infections between 2013 and 2015 in Korea.

    Science.gov (United States)

    Kim, Jeong-Min; Jung, Hee-Dong; Cheong, Hyang-Min; Lee, Anna; Lee, Nam-Joo; Chu, Hyuk; Lee, Joo-Yeon; Kim, Sung Soon; Choi, Jang-Hoon

    2018-07-01

    The prevalence of eight respiratory viruses detected in patients with acute respiratory infections (ARIs) in Korea was investigated through analysis of data recorded by the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) from 2013 to 2015. Nasal aspirate and throat swabs specimens were collected from 36 915 patients with ARIs, and viral nucleic acids were detected by real-time (reverse-transcription) polymerase chain reaction for eight respiratory viruses, including human respiratory syncytial viruses (HRSVs), influenza viruses (IFVs), human parainfluenza viruses (HPIVs), human coronaviruses (HCoVs), human rhinovirus (HRV), human adenovirus (HAdV), human bocavirus (HBoV), and human metapneumovirus (HMPV). The overall positive rate of patient specimens was 49.4% (18 236/36 915), 5% of which carried two or more viruses simultaneously. HRV (15.6%) was the most predominantly detected virus, followed by IFVs (14.6%), HAdV (7.5%), HPIVs (5.8%), HCoVs (4.2%), HRSVs (3.6%), HBoV (1.9%), and HMPV (1.6%). Most of the ARIs were significantly correlated with clinical symptoms of fever, cough, and runny nose. Although HRV and HAdV were frequently detected throughout the year in patients, other respiratory viruses showed apparent seasonality. HRSVs and IFVs were the major causative agents of acute respiratory diseases in infants and young children. Overall, this study demonstrates a meaningful relationship between viral infection and typical manifestations of known clinical features as well as seasonality, age distribution, and co-infection among respiratory viruses. Therefore, these data could provide useful information for public health management and to enhance patient care for primary clinicians. © 2018 Wiley Periodicals, Inc.

  19. [Prevalence of respiratory syncytial virus infection in hospitalized children at a children's hospital and effects of climate change on the prevalence in Suzhou, China].

    Science.gov (United States)

    Geng, Jia; Guo, Wan-Liang; Zhang, Xue-Lan

    2015-05-01

    To investigate the prevalence of respiratory syncytial virus (RSV) infection in hospitalized children and the relationship between the prevalence and the climate change in Suzhou, China. A total of 42 664 nasopharyngeal secretions from hospitalized children with acute respiratory infection at the Suzhou Children's Hospital were screened for RSV antigens using direct immunofluorescence. Monthly meteorological data (mean monthly air temperature, monthly relative humidity, monthly rainfall, total monthly sunshine duration, and mean monthly wind velocity) in Suzhou between 2001 and 2011 were collected. The correlations between RSV detection rate and climatic factors were evaluated using correlation and stepwise regression analysis. The annual RSV infection rate in hospitalized children with respiratory infection in the Suzhou Children's Hospital varied between 11.85% and 27.30% from 2001 to 2011. In the 9 epidemic seasons, each spanning from November to April of the next year, from 2001 to 2010, the RSV detection rates were 40.75%, 22.72%, 39.93%, 27.37%, 42.71%, 21.28%, 38.57%, 19.86%, and 29.73%, respectively; there were significant differences in the detection rate between the epidemic seasons. The monthly RSV detection rate was negatively correlated with mean monthly air temperature, total monthly sunshine duration, monthly rainfall, monthly relative humidity, and mean monthly wind velocity (P<0.05). Stepwise regression analysis showed that mean monthly air temperature fitted into a linear model (R(2)=0.64, P<0.01). From 2001 to 2011, RSV infection in Suzhou was predominantly prevalent between November and April of the next year. As a whole, the infection rate of RSV reached a peak every other year. Air temperature played an important role in the epidemics of RSV infection in Suzhou.

  20. A prospective, open-label, non-comparative study of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus disease in the Russian Federation

    Directory of Open Access Journals (Sweden)

    Turti Tatyana V

    2012-09-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a leading cause of lower respiratory tract infections (LRTIs in children globally. Predisposing conditions for the development of serious RSV disease include preterm infants and those with cardiopulmonary illness, including congenital heart disease (CHD and bronchopulmonary dysplasia (BPD. No vaccine is currently approved for the prevention of RSV infection. It is recommended that children at high risk be prophylactically administered palivizumab, a monoclonal antibody that has been shown in a number of clinical studies to reduce hospitalization rates due to serious RSV infection. The objective of the current study was to determine the safety and effectiveness of palivizumab in preventing serious RSV disease in high-risk children in the Russian Federation. Children at high risk of serious RSV disease (ie, born at ≤35 wk gestational age and ≤6 mo of age, and/or aged ≤24 mo with BPD or hemodynamically significant CHD were enrolled. Subjects were to receive 3 to 5 monthly injections of palivizumab 15 mg/kg (depending on the month of the initial injection over the RSV season. The primary endpoint was RSV-related hospitalizations. Adverse events (AEs were reported through 100 days following the final injection. Results One hundred subjects received ≥1 injection of palivizumab; 94 completed their dosing schedule. There were no RSV hospitalizations or deaths. Six of 7 subjects hospitalized for respiratory/cardiac conditions had an RSV test, which was negative in all cases. Three non-serious AEs (acute intermittent rhinitis and rhinitis, 1 subject; atopic dermatitis, 1 subject were considered possibly related to palivizumab. All other AEs were mild or moderate and considered not related/probably not related to palivizumab. Conclusion Palivizumab was generally well tolerated and effectively prevented serious RSV infection in a mixed population of high-risk children in the Russian

  1. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

    2016-07-15

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  2. Association between the level of antibodies in bulk tank milk and bovine respiratory syncytial virus exposure in the herd.

    Science.gov (United States)

    Klem, T B; Tollersrud, T; Osterås, O; Stokstad, M

    2014-07-12

    Antibody levels in bulk tank milk (BTM) against bovine respiratory syncytial virus (BRSV) are used to classify BRSV status of herds. The aim of this study was to investigate how these levels correspond with the time at which the herds were infected. Bulk tank milk, individual milk and serum samples from cows and young stock were investigated using an indirect ELISA. Screenings of BTM from 89 dairy herds during two winter seasons revealed a prevalence of positive herds from 82 per cent to 85 per cent. Eleven herds showed a marked increase in antibody levels between two screenings, indicating new infection. However, two of these herds had been free from BRSV for the last five to seven years. Two newly infected herds were monitored for four years and did not appear to get reinfected. Surprisingly, the BTM antibody levels in these herds remained high throughout the study period, but fluctuated significantly. This shows that the levels of antibodies in BTM can remain high for several years, even in herds where reinfection does not occur. BTM serology is a useful tool in the monitoring of infectious diseases in dairy herds, but has limitations as a diagnostic tool for BRSV infections. British Veterinary Association.

  3. Neuraminidase treatment of respiratory syncytial virus-infected cells or virions, but not target cells, enhances cell-cell fusion and infection

    International Nuclear Information System (INIS)

    Barretto, Naina; Hallak, Louay K.; Peeples, Mark E.

    2003-01-01

    Respiratory syncytial virus (RSV) infection of HeLa cells induces fusion, but transient expression of the three viral glycoproteins induces fusion poorly, if at all. We found that neuraminidase treatment of RSV-infected cells to remove sialic acid (SA) increases fusion dramatically and that the same treatment of transiently transfected cells expressing the three viral glycoproteins, or even cells expressing the fusion (F) protein alone, results in easily detectable fusion. Neuraminidase treatment of the effector cells, expressing the viral glycoproteins, enhanced fusion while treatment of the target cells did not. Likewise, infectivity was increased by treating virions with neuraminidase, but not by treating target cells. Reduction of charge repulsion by removal of the negatively charged SA is unlikely to explain this effect, since removal of negative charges from either membrane would reduce charge repulsion. Infection with neuraminidase-treated virus remained heparan-sulfate-dependent, indicating that a novel attachment mechanism is not revealed by SA removal. Interestingly, neuraminidase enhancement of RSV infectivity was less pronounced in a virus expressing both the G and the F glycoproteins, compared to virus expressing only the F glycoprotein, possibly suggesting that the G protein sterically hinders access of the neuraminidase to its fusion-enhancing target

  4. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    International Nuclear Information System (INIS)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

    2016-01-01

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  5. A single intranasal immunization with a subunit vaccine formulation induces higher mucosal IgA production than live respiratory syncytial virus

    International Nuclear Information System (INIS)

    Garg, Ravendra; Theaker, Michael; Martinez, Elisa C.; Drunen Littel-van den Hurk, Sylvia van

    2016-01-01

    Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice. This indicates a potential reason as to why long-term immunity is not induced by RSV infection. The comparison also revealed that germinal center lymphocyte populations were higher in ∆F/TriAdj-vaccinated mice. Furthermore, ∆F/TriAdj induced higher gene expression of activation-induced cytidine deaminase (AID), as well as IL-6, IL-21, TGF-β cytokines, which are key players in IgA class switch recombination, ultimately leading to a sustained long-term memory response. - Highlights: •Immune responses to adjuvanted RSV F protein, ∆F/TriAdj, and RSV were compared. •∆F/TriAdj stimulates more local IgA production than RSV. •∆F/TriAdj induces more local IgA secreting memory B cells than RSV. •Germinal center lymphocyte populations are higher in ∆F/TriAdj-vaccinated mice. •∆F/TriAdj induces higher gene expression of AID, IL-6, IL-21, and TGF-β than RSV.

  6. A single intranasal immunization with a subunit vaccine formulation induces higher mucosal IgA production than live respiratory syncytial virus

    Energy Technology Data Exchange (ETDEWEB)

    Garg, Ravendra [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Theaker, Michael [Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Martinez, Elisa C. [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Microbiology & Immunology, University of Saskatchewan, Saskatoon, Canada SK S7N 5E3 (Canada); Drunen Littel-van den Hurk, Sylvia van, E-mail: sylvia.vandenhurk@usask.ca [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada)

    2016-12-15

    Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice. This indicates a potential reason as to why long-term immunity is not induced by RSV infection. The comparison also revealed that germinal center lymphocyte populations were higher in ∆F/TriAdj-vaccinated mice. Furthermore, ∆F/TriAdj induced higher gene expression of activation-induced cytidine deaminase (AID), as well as IL-6, IL-21, TGF-β cytokines, which are key players in IgA class switch recombination, ultimately leading to a sustained long-term memory response. - Highlights: •Immune responses to adjuvanted RSV F protein, ∆F/TriAdj, and RSV were compared. •∆F/TriAdj stimulates more local IgA production than RSV. •∆F/TriAdj induces more local IgA secreting memory B cells than RSV. •Germinal center lymphocyte populations are higher in ∆F/TriAdj-vaccinated mice. •∆F/TriAdj induces higher gene expression of AID, IL-6, IL-21, and TGF-β than RSV.

  7. Bovine respiratory syncytial virus outbreak reduced bulls' weight gain and feed conversion for eight months in a Norwegian beef herd.

    Science.gov (United States)

    Klem, Thea Blystad; Kjæstad, Hans Petter; Kummen, Eiliv; Holen, Hallstein; Stokstad, Maria

    2016-01-25

    Cost-benefit evaluation of measures against respiratory disease in cattle requires accounting with the associated production losses. Investigations of naturally occurring respiratory infections in a herd setting are an opportunity for accurate estimates of the consequences. This article presents estimates based on individual monitoring of weight and concentrate intake of several hundred bulls previous to, during and after a respiratory infection outbreak with bovine respiratory syncytial virus (BRSV) as the main pathogen. The aim of the study was to analyse the association between exposure to BRSV, weight gain and feed conversion rate, quantify any change in these parameters, and estimate the duration of the change in production. A comparison of growth curves for the bulls that were present during the outbreak revealed that bulls with severe clinical signs had a clear and consistent trend of poorer growth rate than those with milder or no signs. The weight/age-ratio was 0.04-0.10 lower in the severely affected bulls, and evident throughout the study period of 8 months. A comparison of growth rates between apparently healthy bulls being present during the outbreak and a comparable group of bulls exactly 1 year later (n = 377) showed a reduced growth rate of 111 g/day in the first group. The difference amounted to 23 extra days needed to reach the reference weight. Feed conversion was also reduced by 79 g weight gain/kilogram concentrate consumed in the outbreak year. This study indicates significant negative effects on performance of animals that develop severe clinical signs in the acute stage, and that the growth and production is negatively affected many months after apparent recovery. In addition, the performance of apparently healthy animals that are exposed during an outbreak are severely negatively affected. The duration of this decrease in production in animals after recovery, or animals that have not shown disease at all, has not previously been

  8. Characteristics and Their Clinical Relevance of Respiratory Syncytial Virus Types and Genotypes Circulating in Northern Italy in Five Consecutive Winter Seasons.

    Directory of Open Access Journals (Sweden)

    Susanna Esposito

    Full Text Available In order to investigate the genetic diversity and patterns of the co-circulating genotypes of respiratory syncytial virus (RSV and their possible relationships with the severity of RSV infection, we studied all of the RSV-positive nasopharyngeal samples collected from children during five consecutive winters (2009-2010, 2010-2011, 2011-2012, 2012-2013 and 2013-2014. The RSVs were detected using the respiratory virus panel fast assay and single-tube RT-PCR, their nucleotides were sequenced, and they were tested for positive selection. Of the 165 positive samples, 131 (79.4% carried RSV-A and 34 (20.6% RSV-B; both groups co-circulated in all of the study periods, with RSV-A predominating in all the seasons except for winter 2010-2011, which had a predominance of RSV-B. Phylogenetic analysis of the RSV-A sequences identified genotypes NA1 and ON1, the second replacing the first during the last two years of the study period. The RSV-B belonged to genotypes BA9 and BA10. BA9 was detected in all the years of the study whereas BA only desultorily. Comparison of the subjects infected by RSV-A and RSV-B types did not reveal any significant differences, but the children infected by genotype A/NA1 more frequently had lower respiratory tract infections (p<0.0001 and required hospitalisation (p = 0.007 more often than those infected by genotype A/ON1. These findings show that RSV has complex patterns of circulation characterised by the periodical replacement of the predominant genotypes, and indicate that the circulation and pathogenic role of the different RSV strains should be investigated as each may have a different impact on the host. A knowledge of the correlations between types, genotypes and disease severity may also be important in order to be able to include the more virulent strains in future vaccines.

  9. The relationship between antibody status to bovine corona virus and bovine respiratory syncytial virus and disease incidence, reproduction and herd characteristics in dairy herds

    Directory of Open Access Journals (Sweden)

    Tråvén Madeleine

    2010-06-01

    Full Text Available Abstract Background Bovine respiratory syncytial virus (BRSV and bovine corona virus (BCV affects cattle worldwide. Our objective was to evaluate the effects of these infections on general health and reproduction parameters measurable on herd level and to explore the association between antibody status and some herd characteristics. Methods We collected a pooled milk sample from five primiparous cows from 79 Swedish dairy herds in September 2006. The samples were analysed for immunoglobulin G antibodies to BCV and BRSV with indirect enzyme-linked immunosorbent assays. Herd level data from 1 September 2005 to 30 August 2006 were accessed retrospectively. The location of the herds was mapped using a geographical information system. Results Ten herds were antibody negative to both viruses and were compared with 69 herds positive to BCV or BRSV or both. Positive herds had a higher (P = 0.001 bulk tank milk somatic cell count (BMSCC compared with negative herds. The medians for all other analyzed health and reproductive parameters were consistently in favour of the herds negative to both viruses although the differences were not statistically significant. A higher proportion (P = 0.01 of herds used professional technicians for artificial insemination, rather than farm personnel, amongst the 33 herds negative to BCV compared with the 46 positive herds. Conclusions Our result shows that herds that were antibody positive to BCV and/or BRSV had a higher BMSCC compared with herds negative to BCV and BRSV. There was also tendency that negative herds had a better general herd health compared with positive. A higher proportion amongst the BCV negative herds used external technicians for AI instead of farm personnel, indicating that it is possible to avoid infection although having regular visits. Negative herds were located in close proximity to positive herds, indicating that local spread and airborne transmission between herds might not be of great

  10. Seasonality of Influenza and Respiratory Syncytial Viruses and the Effect of Climate Factors in Subtropical-Tropical Asia Using Influenza-Like Illness Surveillance Data, 2010 -2012.

    Science.gov (United States)

    Kamigaki, Taro; Chaw, Liling; Tan, Alvin G; Tamaki, Raita; Alday, Portia P; Javier, Jenaline B; Olveda, Remigio M; Oshitani, Hitoshi; Tallo, Veronica L

    2016-01-01

    The seasonality of influenza and respiratory syncytial virus (RSV) is well known, and many analyses have been conducted in temperate countries; however, this is still not well understood in tropical countries. Previous studies suggest that climate factors are involved in the seasonality of these viruses. However, the extent of the effect of each climate variable is yet to be defined. We investigated the pattern of seasonality and the effect of climate variables on influenza and RSV at three sites of different latitudes: the Eastern Visayas region and Baguio City in the Philippines, and Okinawa Prefecture in Japan. Wavelet analysis and the dynamic linear regression model were applied. Climate variables used in the analysis included mean temperature, relative and specific humidity, precipitation, and number of rainy days. The Akaike Information Criterion estimated in each model was used to test the improvement of fit in comparison with the baseline model. At all three study sites, annual seasonal peaks were observed in influenza A and RSV; peaks were unclear for influenza B. Ranges of climate variables at the two Philippine sites were narrower and mean variables were significantly different among the three sites. Whereas all climate variables except the number of rainy days improved model fit to the local trend model, their contributions were modest. Mean temperature and specific humidity were positively associated with influenza and RSV at the Philippine sites and negatively associated with influenza A in Okinawa. Precipitation also improved model fit for influenza and RSV at both Philippine sites, except for the influenza A model in the Eastern Visayas. Annual seasonal peaks were observed for influenza A and RSV but were less clear for influenza B at all three study sites. Including additional data from subsequent more years would help to ascertain these findings. Annual amplitude and variation in climate variables are more important than their absolute values for

  11. Seasonality of Influenza and Respiratory Syncytial Viruses and the Effect of Climate Factors in Subtropical-Tropical Asia Using Influenza-Like Illness Surveillance Data, 2010 -2012.

    Directory of Open Access Journals (Sweden)

    Taro Kamigaki

    Full Text Available The seasonality of influenza and respiratory syncytial virus (RSV is well known, and many analyses have been conducted in temperate countries; however, this is still not well understood in tropical countries. Previous studies suggest that climate factors are involved in the seasonality of these viruses. However, the extent of the effect of each climate variable is yet to be defined.We investigated the pattern of seasonality and the effect of climate variables on influenza and RSV at three sites of different latitudes: the Eastern Visayas region and Baguio City in the Philippines, and Okinawa Prefecture in Japan. Wavelet analysis and the dynamic linear regression model were applied. Climate variables used in the analysis included mean temperature, relative and specific humidity, precipitation, and number of rainy days. The Akaike Information Criterion estimated in each model was used to test the improvement of fit in comparison with the baseline model.At all three study sites, annual seasonal peaks were observed in influenza A and RSV; peaks were unclear for influenza B. Ranges of climate variables at the two Philippine sites were narrower and mean variables were significantly different among the three sites. Whereas all climate variables except the number of rainy days improved model fit to the local trend model, their contributions were modest. Mean temperature and specific humidity were positively associated with influenza and RSV at the Philippine sites and negatively associated with influenza A in Okinawa. Precipitation also improved model fit for influenza and RSV at both Philippine sites, except for the influenza A model in the Eastern Visayas.Annual seasonal peaks were observed for influenza A and RSV but were less clear for influenza B at all three study sites. Including additional data from subsequent more years would help to ascertain these findings. Annual amplitude and variation in climate variables are more important than their

  12. Structure and functional analysis of the RNA- and viral phosphoprotein-binding domain of respiratory syncytial virus M2-1 protein.

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    Marie-Lise Blondot

    Full Text Available Respiratory syncytial virus (RSV protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties are related to the core region of M2-1 encompassing residues S58 to K177. Here we report the NMR structure of the RSV M2-1(58-177 core domain, which is structurally homologous to the C-terminal domain of Ebola virus VP30, a transcription co-factor sharing functional similarity with M2-1. The partial overlap of RNA and P interaction surfaces on M2-1(58-177, as determined by NMR, rationalizes the previously observed competitive behavior of RNA versus P. Using site-directed mutagenesis, we identified eight residues located on these surfaces that are critical for an efficient transcription activity of the RdRp complex. Single mutations of these residues disrupted specifically either P or RNA binding to M2-1 in vitro. M2-1 recruitment to cytoplasmic inclusion bodies, which are regarded as sites of viral RNA synthesis, was impaired by mutations affecting only binding to P, but not to RNA, suggesting that M2-1 is associated to the holonucleocapsid by interacting with P. These results reveal that RNA and P binding to M2-1 can be uncoupled and that both are critical for the transcriptional antitermination function of M2-1.

  13. Comparison of the Simplexa™ Flu A/B & RSV kit (nucleic acid extraction-dependent assay) and the Prodessa ProFlu+™ assay for detecting influenza and respiratory syncytial viruses.

    Science.gov (United States)

    Selvaraju, Suresh B; Bambach, Adrienne V; Leber, Amy L; Patru, Maria-Magdalena; Patel, Anami; Menegus, Marilyn A

    2014-09-01

    The relative performance of 2 widely used reverse transcription polymerase chain reaction (RT-PCR) assays, the Focus diagnostics Simplexa™ Flu A/B & RSV kit (nucleic acid extraction-dependent assay) and the Prodessa Proflu+™ assay, was evaluated using 735 prospectively and retrospectively collected nasopharyngeal swab specimens. Overall, the assays showed positive and negative agreements of 100% and 99.7% for influenza A, 98.1% and 99.9% for influenza B, and 99.3% and 99.5% for respiratory syncytial virus. The relative analytical sensitivity of the 2 assays was also similar. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Use of palivizumab and infection control measures to control an outbreak of respiratory syncytial virus in a neonatal intensive care unit confirmed by real-time polymerase chain reaction.

    LENUS (Irish Health Repository)

    O'Connell, K

    2011-04-01

    Respiratory syncytial virus (RSV) is a potentially life-threatening infection in premature infants. We report an outbreak involving four infants in the neonatal intensive care unit (NICU) of our hospital that occurred in February 2010. RSV A infection was confirmed by real-time polymerase chain reaction. Palivizumab was administered to all infants in the NICU. There were no additional symptomatic cases and repeat RSV surveillance confirmed that there was no further cross-transmission within the unit. The outbreak highlighted the infection control challenge of very high bed occupancy in the unit and the usefulness of molecular methods in facilitating detection and management.

  15. Trends in Respiratory Syncytial Virus and Bronchiolitis Hospitalization Rates in High-Risk Infants in a United States Nationally Representative Database, 1997-2012.

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    Abigail Doucette

    Full Text Available Respiratory syncytial virus (RSV causes significant pediatric morbidity and is the most common cause of bronchiolitis. Bronchiolitis hospitalizations declined among US infants from 2000‒2009; however, rates in infants at high risk for RSV have not been described. This study examined RSV and unspecified bronchiolitis (UB hospitalization rates from 1997‒2012 among US high-risk infants.The Kids' Inpatient Database (KID infant annual RSV (ICD-9 079.6, 466.11, 480.1 and UB (ICD-9 466.19, 466.1 hospitalization rates were estimated using weighted counts. Denominators were based on birth hospitalizations with conditions associated with high-risk for RSV: chronic perinatal respiratory disease (chronic lung disease [CLD]; congenital airway anomalies (CAA; congenital heart disease (CHD; Down syndrome (DS; and other genetic, metabolic, musculoskeletal, and immunodeficiency conditions. Preterm infants could not be identified. Hospitalizations were characterized by mechanical ventilation, inpatient mortality, length of stay, and total cost (2015$. Poisson and linear regression were used to test statistical significance of trends.RSV and UB hospitalization rates were substantially elevated for infants with higher-risk CHD, CLD, CAA and DS without CHD compared with all infants. RSV rates declined by 47.0% in CLD and 49.7% in higher-risk CHD infants; no other declines in high-risk groups were observed. UB rates increased in all high-risk groups except for a 22.5% decrease among higher-risk CHD. Among high-risk infants, mechanical ventilation increased through 2012 to 20.4% and 13.5% of RSV and UB hospitalizations; geometric mean cost increased to $31,742 and $25,962, respectively, and RSV mortality declined to 0.9%.Among high-risk infants between 1997 and 2012, RSV hospitalization rates declined among CLD and higher-risk CHD infants, coincident with widespread RSV immunoprophylaxis use in these populations. UB hospitalization rates increased in all high

  16. [Differentiation of influenza (Flu) type A, type B, and respiratory syncytial virus (RSV) by QuickNavi™-Flu+RSV].

    Science.gov (United States)

    Kohiyama, Risa; Miyazawa, Takashi; Shibano, Nobuko; Inano, Koichi

    2014-01-01

    Because it is not easy to differentiate Influenza virus (Flu) from RS virus (RSV) just by clinical symptoms, to accurately diagnose those viruses in conjunction with patient's clinical symptoms, rapid diagnostic kits has been used separately for each of those viruses. In our new study, we have developed a new rapid diagnostic kit, QuickNavi™-Flu+RSV. The kit can detect Flu A, Flu B, and RSV antigens with a single sample collection and an assay. Total of 2,873 cases (including nasopharyngeal swabs and nasopharyngeal aspirates specimens) in 2010/2011 and 2011/2012 seasons were evaluated with QuickNavi™-Flu+RSV and a commercially available kit. Sensitivity, specificity, and accuracy of Flu type A, type B, and RSV were above 95% when compared to commercially available kits (QuickNavi™-Flu and QuickNavi™-RSV) and considered to be equivalent to the commercially available kits. In 2011/2012 season, RSV infections increased prior to Flu season and continued during the peak of the Flu season. The kit can contribute to accurate diagnosis of Flu and RSV infections since co-infection cases have also been reported during the 2011/2012 season. QuickNavi™-Flu+RSV is useful for differential diagnosis of respiratory infectious diseases since it can detect Flu type A, type B, and RSV virus antigens with a single sample collection.

  17. Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial

    Science.gov (United States)

    Nolan, Terry; Borja-Tabora, Charissa; Lopez, Pio; Weckx, Lily; Ulloa-Gutierrez, Rolando; Lazcano-Ponce, Eduardo; Kerdpanich, Angkool; Weber, Miguel Angel Rodriguez; Mascareñas de Los Santos, Abiel; Tinoco, Juan-Carlos; Safadi, Marco Aurelio P.; Seng, Lim Fong; Hernandez-de Mezerville, Marcela; Faingezicht, Idis; Cruz-Valdez, Aurelio; Feng, Yang; Li, Ping; Durviaux, Serge; Haars, Gerco; Roy-Ghanta, Sumita; Vaughn, David W.; Taylor, Sylvia

    2015-01-01

    Background. The high burden of respiratory syncytial virus (RSV)-associated morbidity and mortality makes vaccine development a priority. Methods. As part of an efficacy trial of pandemic influenza vaccines (NCT01051661), RSV epidemiology in healthy children aged 6 months to <10 years at first vaccination with influenza-like illness (ILI) was evaluated in Australia, Brazil, Colombia, Costa Rica, Mexico, the Philippines, Singapore, and Thailand between February 2010 and August 2011. Active surveillance for ILI was conducted for approximately 1 year, with nasal and throat swabs analyzed by polymerase chain reaction. The prevalence and incidence of RSV among ILI episodes were calculated. Results. A total of 6266 children were included, of whom 2421 experienced 3717 ILI episodes with a respiratory sample available. RSV was detected for 359 ILI episodes, a prevalence of 9.7% (95% confidence interval: 8.7–10.7). The highest prevalence was in children aged 12–23 or 24–35 months in all countries except the Philippines, where it was in children aged 6–11 months. The incidence of RSV-associated ILI was 7.0 (6.3–7.7) per 100 person-years (PY). Eighty-eight ILI episodes resulted in hospitalization, of which 8 were associated with RSV (prevalence 9.1% [4.0–17.1]; incidence 0.2 [0.1–0.3] per 100 PY). The incidence of RSV-associated ILI resulting in medical attendance was 6.0 (5.4–6.7) per 100 PY. RSV B subtypes were observed more frequently than A subtypes. Conclusions. Active surveillance demonstrated the considerable burden of RSV-associated illness that would not be identified through hospital-based surveillance, with a substantial part of the burden occurring in older infants and children. PMID:25673560

  18. Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity.

    Science.gov (United States)

    Pancham, Krishna; Sami, Iman; Perez, Geovanny F; Huseni, Shehlanoor; Kurdi, Bassem; Rose, Mary C; Rodriguez-Martinez, Carlos E; Nino, Gustavo

    2016-02-01

    Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same family as that of respiratory syncytial virus (RSV). Premature children are at high risk of severe RSV infections, however, it is unclear whether HMPV infection is more severe in hospitalized children with a history of severe prematurity. We conducted a retrospective analysis of the clinical respiratory presentation of all polymerase chain reaction-confirmed HMPV infections in preschool-age children (≤5 years) with and without history of severe prematurity (prematurity. Preschool children with a history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity, and history of asthma. Our study suggests that HMPV infection causes significant disease burden among preschool children with a history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations. Copyright © 2016. Published by Elsevier B.V.

  19. Respiratory syncytial virus and TNFalpha induction of chemokine gene expression involves differential activation of Rel A and NF-kappaB1

    Directory of Open Access Journals (Sweden)

    Roebuck Kenneth A

    2002-03-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV infection of airway epithelial cells stimulates the expression and secretion of a variety of cytokines including the chemotactic cytokines interleukin-8 (IL-8, monocyte chemoattractant protein-1 (MCP-1, and RANTES (regulated upon activation, normal T cell expressed and secreted. Chemokines are important chemoattractants for the recruitment of distinct sets of leukocytes to airway sites of inflammation. Results We have shown previously that chemokine expression is regulated in airway epithelial cells (A549 in a stimulus-specific manner in part through the redox-responsive transcription factors AP-1 and NF-κB. In this study, we examined the NF-κB-mediated effects of RSV and the proinflammatory cytokine TNFα on the induction of IL-8, MCP-1 and RANTES chemokine gene expression in A549 epithelial cells. The results demonstrate that RSV induces chemokine expression with distinct kinetics that is associated with a specific pattern of NF-κB binding activity. This distinction was further demonstrated by the differential effects of the NF-κB inhibitors dexamethasone (DEX and N-acetyl-L-cysteine (NAC. NAC preferentially inhibited RSV induced chemokine expression, whereas DEX preferentially inhibited TNFα induced chemokine expression. DNA binding studies using NF-κB subunit specific binding ELISA demonstrated that RSV and TNFα induced different NF-κB binding complexes containing Rel A (p65 and NF-κB1 (p50. Both TNFα and RSV strongly induced Rel A the activation subunit of NF-κB, whereas only TNFα was able to substantially induce the p50 subunit. Consistent with the expression studies, RSV but not TNFα induction of Rel A and p50 were markedly inhibited by NAC, providing a mechanism by which TNFα and RSV can differentially activate chemokine gene expression via NF-κB. Conclusions These data suggest that RSV induction of chemokine gene expression, in contrast to TNFα, involves redox

  20. Burden of paediatric respiratory syncytial virus disease and potential effect of different immunisation strategies: a modelling and cost-effectiveness analysis for England.

    Science.gov (United States)

    Cromer, Deborah; van Hoek, Albert Jan; Newall, Anthony T; Pollard, Andrew J; Jit, Mark

    2017-08-01

    Vaccines and prophylactic antibodies against respiratory syncytial virus (RSV) are in development and likely to be available in the next 5-10 years. The most efficient way to use these products when they become available is an important consideration for public health decision makers. We performed a multivariate regression analysis to estimate the burden of RSV in children younger than 5 years in England (UK), a representative high-income temperate country, and used these results to assess the potential effect of different RSV immunisation strategies (targeting vaccination for infants, or pregnant women, or prophylactic antibodies for neonates). We did a cost-effectiveness analysis for these strategies, implemented either separately or concurrently, and assessed the effect of restricting vaccination to certain months of the year. We estimated that RSV is responsible for 12 primary care consultations (95% CI 11·9-12·1) and 0·9 admissions to hospital annually per 100 children younger than 5 years (95% CI 0·89-0·90), with the major burden occurring in infants younger than 6 months. The most cost-effective strategy was to selectively immunise all children born before the start of the RSV season (maximum price of £220 [95% uncertainty interval (UI) 208-232] per vaccine, for an incremental cost-effectiveness ratio of £20 000 per quality-adjusted life-year). The maximum price per fully protected person that should be paid for the infant, newborn, and maternal strategies without seasonal restrictions was £192 (95% UI 168-219), £81 (76-86), and £54 (51-57), respectively. Nearly double the number of primary care consultations, and nearly five times the number of admissions to hospital occurred with RSV compared with influenza. RSV vaccine and antibody strategies are likely to be cost-effective if they can be priced below around £200 per fully protected person. A seasonal vaccination strategy is likely to provide the most direct benefits. Herd effects might

  1. A novel six consecutive monthly doses of palivizumab prophylaxis protocol for the prevention of respiratory syncytial virus infection in high-risk preterm infants in Taiwan.

    Directory of Open Access Journals (Sweden)

    Hsin Chi

    Full Text Available Respiratory syncytial virus (RSV circulates year round in Taiwan. A novel six consecutive monthly doses of palivizumab for RSV prevention protocol has been approved for high risk preterm infants since December 2010. This study aimed to determine the clinical effectiveness and safety of this novel protocol for the prevention of RSV infection.From April 2011 to March 2013, we enrolled infants born at ≤28 weeks gestation and infants born at ≤35 weeks gestation with chronic lung disease (CLD who received palivizumab prophylaxis as study group and followed up for 12 months. Historic control, those who were born and followed up between July 2000 and June 2008, were retrieved for propensity score matching. Primary endpoint was RSV-related hospitalization, and secondary endpoints included the length of hospital stay and intensive care unit (ICU care.We enrolled 127 infants (108 infants born at ≤28 weeks and 19 infants born at 29-35 weeks with CLD. They completed 6-dose palivizumab as scheduled. Among the study group, the RSV-related hospitalizations were 2 (1.6% within 6 months and 5 (3.9% within 12 months after discharge. We matched 127 infants in the control group with 127 infants in the study group by propensity score matching. The reduction of RSV-related hospitalization rates were 86% (10.2% vs 1.6%, p = 0.002 within 6 months after discharge and 78% (15.7% vs 3.9%, p = 0.004 within 12 months after discharge. Compared to the control group, the rate of ICU care significantly decreased from 7.1% to 0.8% (p = 0.024 within 6 months after discharge and from 7.9% to 0.8% (p = 0.014 within 12 months after discharge. Adverse events were recorded in 6.4% injections.Six monthly intramuscular administration of palivizumab is effective for prevention of RSV hospitalization in regions with no single seasonal peak of RSV infection such as Taiwan.

  2. Respiratory syncytial virus infection in sheep bronchial explants is associated with enhanced ETB receptor-mediate contractile functional and autoradiographic studies

    International Nuclear Information System (INIS)

    Fernandes, L.B.; D'Aprile, A.C.; Betts, R.J.; Goldie, R.G.

    2001-01-01

    Full text: Respiratory syncytial virus (RSV) is an important precipitant of asthma in children. The impact of RSV infection on endothelin (ET) receptor density and function in airways is unknown. In the present study, sheep bronchial rings were maintained as explants in culture for up to 48 h. During this time, both the structural integrity of the epithelium and carbachol responsiveness were preserved. Bronchial rings in culture were exposed to non-infected culture medium or to RSV (1/50 TCID 50 ) for 0, 24 and 48 h which caused marked damage to and loss of the epithelium. RSV infection did not significantly alter responsiveness to ET-1 at either 24 (Control EC 40 = 102 nM, 95% confidence limits, 76-138 nM vs RSV EC 40 = 66 nM, 95% confidence limits, 48-91 nM, n=5-6, P>0.05) or 48 h (Control EC 40 35 nM, 95% confidence limits, 19-66 nM vs RSV EC 40 = 55 nM, 95% confidence limits, 32-93 nM, n=8, P>0.05). As seen previously (Goldie et al., 1994), sarafotoxin S6c (StxS6c, ET B -selective) did not cause contraction in non-infected sheep bronchial explants. In contrast, StxS6c (300 nM) increased tone by 8±3% carbachol Emax (n=6-8) in explants exposed to RSV for 24 or 48 h. Light microscopic autoradiography was used to determine the relative distribution of ET A and ET B receptors using [ 125 I]-ET-1, BQ-123 (ET A -selective) and StxS6c. Sheep airway smooth muscle contains a homogeneous population of ET A receptors (Goldie et al., 1994). Since StxS6c caused significant contraction in RSV-infected bronchial explants, it was surprising that autoradiographic techniques failed to detect airway smooth muscle ET B receptors in these preparations. It is likely that ET B receptors fell below the level of detection of autoradiography. The significant StxS6c-induced contraction of sheep bronchi suggests the novel expression of ET B receptors triggered by RSV which might be relevant to RSV-associated asthma. Copyright (2001) Australasian Society of Clinical and Experimental

  3. Cost-utility analysis of Palivizumab for Respiratory Syncytial Virus infection prophylaxis in preterm infants: update based on the clinical evidence in Spain.

    Science.gov (United States)

    Sanchez-Luna, M; Burgos-Pol, R; Oyagüez, I; Figueras-Aloy, J; Sánchez-Solís, M; Martinón-Torres, F; Carbonell-Estrany, X

    2017-10-17

    This study aimed at estimating the efficiency of palivizumab in the prevention of Respiratory Syncytial Virus (RSV) infection and its sequelae in preterm infants (32 day 1 -35 day 0 weeks of gestational age -wGA-) in Spain. A decision-tree model was developed to compare health benefits (Quality Adjusted Life Years-QALYs) and costs of palivizumab versus a non-prophylaxis strategy over 6 years. A hypothetical cohort of 1,000 preterm infants, 32 day 1 -35 day 0 wGA (4.356 kg average weight) at the beginning of the prophylaxis (15 mg/kg of palivizumab; 3.88 average number of injections per RSV season) was analysed. The model considered the most recent evidence from Spanish observational and epidemiological studies on RSV infection: the FLIP II study provided hospital admission and Intensive Care Unit (ICU) admission rates; in-hospital mortality rate was drawn from an epidemiological study from 2004 to 2012; recurrent wheezing rates associated to RSV infection from SPRING study were adjusted by the evidence on the palivizumab effect from clinical trials. Quality of life baseline value, number of hospitalized infants and the presence of recurrent wheezing over time were granted to estimate QALYs. National Health Service and societal perspective (included also recurrent wheezing indirect cost) were analysed. Total costs (€, 2016) included pharmaceutical and administration costs, hospitalization costs and recurrent wheezing management annual costs. A discount rate of 3.0% was applied annually for both costs and health outcomes. Over 6 years, the base case analysis showed that palivizumab was associated to an increase of 0.0731 QALYs compared to non-prophylaxis. Total costs were estimated in €2,110.71 (palivizumab) and €671.68 (non-prophylaxis) from the National Health System (NHS) perspective, resulting in an incremental cost utility ratio (ICUR) of €19,697.69/QALYs gained (prophylaxis vs non-prophylaxis). Results derived from the risk-factors population

  4. New ICRP human respiratory tract model

    International Nuclear Information System (INIS)

    Bailey, M.R.

    1993-01-01

    The new ICRP dosimetric model for the human respiratory tract is based on the premise that the large differences in radiation sensitivity of respiratory tract tissues, and the wide range of doses they receive argue for calculating specific tissue doses rather than average lung doses. The model is also directly applicable to the worldwide population of both workers and the public. The requirement to describe intake, and deposition, clearance and dosimetry in each respiratory tract region, for a wide range of subjects at various levels of exercise necessarily means that the model is more complex than that of ICRP Publication 30. The widespread use of powerful personal computers, and the availability of user-friendly software to implement the model, however, will make it widely and readily accessible when the report is published. (Author)

  5. Ocular Tropism of Respiratory Viruses

    Science.gov (United States)

    Rota, Paul A.; Tumpey, Terrence M.

    2013-01-01

    SUMMARY Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism. PMID:23471620

  6. Human bocavirus infection as a cause of severe acute respiratory tract infection in children.

    Science.gov (United States)

    Moesker, F M; van Kampen, J J A; van der Eijk, A A; van Rossum, A M C; de Hoog, M; Schutten, M; Smits, S L; Bodewes, R; Osterhaus, A D M E; Fraaij, P L A

    2015-10-01

    In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Respiratory Syncytial Virus (RSV): Treatment

    Science.gov (United States)

    ... Relations Cyber Infrastructure Computational Biology Equal Employment Opportunity Ethics Global Research Office of Mission Integration and Financial Management Strategic Planning Workforce Effectiveness Workplace Solutions Technology Transfer Intellectual Property Division of AIDS ...

  8. Evidence that maturation of the N-linked glycans of the respiratory syncytial virus (RSV) glycoproteins is required for virus-mediated cell fusion: The effect of α-mannosidase inhibitors on RSV infectivity

    International Nuclear Information System (INIS)

    McDonald, Terence P.; Jeffree, Chris E.; Li, Ping; Rixon, Helen W. McL.; Brown, Gaie; Aitken, James D.; MacLellan, Kirsty; Sugrue, Richard J.

    2006-01-01

    Glycan heterogeneity of the respiratory syncytial virus (RSV) fusion (F) protein was demonstrated by proteomics. The effect of maturation of the virus glycoproteins-associated glycans on virus infectivity was therefore examined using the α-mannosidase inhibitors deoxymannojirimycin (DMJ) and swainsonine (SW). In the presence of SW the N-linked glycans on the F protein appeared in a partially mature form, whereas in the presence of DMJ no maturation of the glycans was observed. Neither inhibitor had a significant effect on G protein processing or on the formation of progeny virus. Although the level of infectious virus and syncytia formation was not significantly affected by SW-treatment, DMJ-treatment correlated with a one hundred-fold reduction in virus infectivity. Our data suggest that glycan maturation of the RSV glycoproteins, in particular those on the F protein, is an important step in virus maturation and is required for virus infectivity

  9. 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.

  10. Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures.

    Science.gov (United States)

    Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline

    2018-06-01

    The leading cause of acute illnesses, respiratory viruses, typically cause self-limited diseases, although severe complications can occur in fragile patients. Rhinoviruses (RVs), respiratory enteroviruses (EVs), influenza virus, respiratory syncytial viruses (RSVs), and coronaviruses are highly prevalent respiratory pathogens, but because of the lack of reliable animal models, their differential pathogenesis remains poorly characterized. We sought to compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Tissues were infected with RV-A55, RV-A49, RV-B48, RV-C8, and RV-C15; respiratory EV-D68; influenza virus H3N2; RSV-B; and human coronavirus (HCoV)-OC43. Replication kinetics, cell tropism, effect on tissue integrity, and cytokine secretion were compared. Viral adaptation and tissue response were assessed through RNA sequencing. RVs, RSV-B, and HCoV-OC43 infected ciliated cells and caused no major cell death, whereas H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses, except RV-B48 and HCoV-OC43, altered cilia beating and mucociliary clearance. H3N2 was the strongest cytokine inducer, and HCoV-OC43 was the weakest. Persistent infection was observed in all cases. RNA sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4 days after infection. No majority mutations emerged in the viral population. Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory tract infections in immunocompromised hosts. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Palivizumab for immunoprophylaxis of respiratory syncytial virus (RSV) bronchiolitis in high-risk infants and young children: a systematic review and additional economic modelling of subgroup analyses.

    Science.gov (United States)

    Wang, D; Bayliss, S; Meads, C

    2011-01-01

    Respiratory syncytial virus (RSV) is a seasonal infectious disease, with epidemics occurring annually from October to March in the UK. It is a very common infection in infants and young children and can lead to hospitalisation, particularly in those who are premature or who have chronic lung disease (CLD) or congenital heart disease (CHD). Palivizumab (Synagis®, MedImmune) is a monoclonal antibody designed to provide passive immunity against RSV and thereby prevent or reduce the severity of RSV infection. It is licensed for the prevention of serious lower respiratory tract infection caused by RSV in children at high risk. While it is recognised that a policy of using palivizumab for all children who meet the licensed indication does not meet conventional UK standards of cost-effectiveness, most clinicians feel that its use is justified in some children. To use systematic review evidence to estimate the cost-effectiveness of immunoprophylaxis of RSV using palivizumab in different subgroups of children with or without CLD or CHD who are at high risk of serious morbidity from RSV infection. A systematic review of the literature and an economic evaluation was carried out. The bibliographic databases included the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] and five other databases, from inception to 2009. Research registries of ongoing trials including Current Controlled Trials metaRegister, Clinical Trials.gov and the National Institute for Health Research Clinical Research Network Portfolio were also searched. Searches were conducted for prognostic and hospitalisation studies covering 1950-2009 (the original report searches conducted in 2007 covering the period 1950-2007 were rerun in August 2009 to cover the period 2007-9) and the database of all references from the original report was sifted to

  12. Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Ahmed A. Abdulhaq

    2017-01-01

    Full Text Available We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time. Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2% of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV was the most detected pathogen (40.9% followed by non-MERS-CoV human coronaviruses (19.3%, influenza (Flu viruses (15.9%, and human respiratory syncytial virus (hRSV (13.6%. Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control.

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

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    María Luz García-García

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

  14. A Review on Human Respiratory Modeling.

    Science.gov (United States)

    Ghafarian, Pardis; Jamaati, Hamidreza; Hashemian, Seyed Mohammadreza

    2016-01-01

    Input impedance of the respiratory system is measured by forced oscillation technique (FOT). Multiple prior studies have attempted to match the electromechanical models of the respiratory system to impedance data. Since the mechanical behavior of airways and the respiratory system as a whole are similar to an electrical circuit in a combination of series and parallel formats some theories were introduced according to this issue. It should be noted that, the number of elements used in these models might be less than those required due to the complexity of the pulmonary-chest wall anatomy. Various respiratory models have been proposed based on this idea in order to demonstrate and assess the different parts of respiratory system related to children and adults data. With regard to our knowledge, some of famous respiratory models in related to obstructive, restrictive diseases and also Acute Respiratory Distress Syndrome (ARDS) are reviewed in this article.

  15. Quantification and determinants of the amount of respiratory syncytial virus (RSV shed using real time PCR data from a longitudinal household study [version 2; referees: 2 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Miriam Wathuo

    2017-03-01

    Full Text Available Background A better understanding of respiratory syncytial virus (RSV epidemiology requires realistic estimates of RSV shedding patterns, quantities shed, and identification of the related underlying factors. Methods RSV infection data arise from a cohort study of 47 households with 493 occupants, in coastal Kenya, during the 2009/2010 RSV season. Nasopharyngeal swabs were taken every 3 to 4 days and screened for RSV using a real time polymerase chain reaction (PCR assay. The amount of virus shed was quantified by calculating the ‘area under the curve’ using the trapezoidal rule applied to rescaled PCR cycle threshold output. Multivariable linear regression was used to identify correlates of amount of virus shed. Results The median quantity of virus shed per infection episode was 29.4 (95% CI: 15.2, 54.2 log10 ribonucleic acid (RNA copies * days. Young age (<1 year, presence of upper respiratory symptoms, intra-household acquisition of infection, an individual’s first infection episode in the RSV season, and having a co-infection of RSV group A and B were associated with increased amount of virus shed. Conclusions The findings provide insight into which groups of individuals have higher potential for transmission, information which may be useful in designing RSV prevention strategies.

  16. Incidence and etiology of hospitalized acute respiratory infections in the Egyptian Delta

    OpenAIRE

    Rowlinson, Emily; Dueger, Erica; Mansour, Adel; Azzazy, Nahed; Mansour, Hoda; Peters, Lisa; Rosenstock, Summer; Hamid, Sarah; Said, Mayar M.; Geneidy, Mohamed; Abd Allah, Monier; Kandeel, Amr

    2016-01-01

    Introduction Acute Respiratory Infections (ARI) are responsible for nearly two million childhood deaths worldwide. A limited number of studies have been published on the epidemiology of viral respiratory pathogens in Egypt. Methods A total of 6113 hospitalized patients >1?month of age with suspected ARI were enrolled between June 23, 2009 and December 31, 2013. Naso? and oropharyngeal specimens were collected and tested for influenza A and B, respiratory syncytial virus, human metapneumovirus...

  17. Correction to: Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan.

    Science.gov (United States)

    Kashiwagi, Tomoko; Okada, Yukiko; Nomoto, Ken

    2018-06-01

    "Newborns, infants, or young children aged 24 months and under who have Down syndrome, and children ≤ 24 months of age without a current hs-CHD if they had experienced persistent respiratory symptoms or regular outpatient treatment due to a respiratory tract infection in previous RSV seasons were also eligible for the study."

  18. Human herpesviruses respiratory infections in patients with acute respiratory distress (ARDS).

    Science.gov (United States)

    Bonizzoli, Manuela; Arvia, Rosaria; di Valvasone, Simona; Liotta, Francesco; Zakrzewska, Krystyna; Azzi, Alberta; Peris, Adriano

    2016-08-01

    Acute respiratory distress syndrome (ARDS) is today a leading cause of hospitalization in intensive care unit (ICU). ARDS and pneumonia are closely related to critically ill patients; however, the etiologic agent is not always identified. The presence of human herpes simplex virus 1, human cytomegalovirus and Epstein-Barr virus in respiratory samples of critically ill patients is increasingly reported even without canonical immunosuppression. The main aim of this study was to better understand the significance of herpesviruses finding in lower respiratory tract of ARDS patients hospitalized in ICU. The presence of this group of herpesviruses, in addition to the research of influenza viruses and other common respiratory viruses, was investigated in respiratory samples from 54 patients hospitalized in ICU, without a known microbiological causative agent. Moreover, the immunophenotype of each patient was analyzed. Herpesviruses DNA presence in the lower respiratory tract seemed not attributable to an impaired immunophenotype, whereas a significant correlation was observed between herpesviruses positivity and influenza virus infection. A higher ICU mortality was significantly related to the presence of herpesvirus infection in the lower respiratory tract as well as to impaired immunophenotype, as patients with poor outcome showed severe lymphopenia, affecting in particular T (CD3+) cells, since the first days of ICU hospitalization. In conclusion, these results indicate that herpesviruses lower respiratory tract infection, which occurs more frequently following influenza virus infection, can be a negative prognostic marker. An independent risk factor for ICU patients with ARDS is an impaired immunophenotype.

  19. Prevalence of human rhinovirus in children admitted to hospital with acute lower respiratory tract infections in Changsha, China.

    Science.gov (United States)

    Zeng, Sai-Zhen; Xiao, Ni-Guang; Xie, Zhi-Ping; Xie, Guang-Cheng; Zhong, Li-Li; Wang, Juan; Huang, Han; Zhang, Bing; Duan, Zhao-Jun

    2014-11-01

    Human rhinovirus (HRV) is a causative agent of acute respiratory tract infections. This study analyzed the prevalence and clinical characteristics of three HRV groups (HRV-A, -B, and -C) among 1,165 children aged 14 years or younger who were hospitalized with acute lower respiratory tract infection in China. PCR or reverse transcription-PCR was performed to detect 14 respiratory viruses in nasopharyngeal aspirates collected from September 2007 to August 2008 in Changsha, China. HRV was detected in 202 (17.3%) of the 1,165 children; 25.3% of the HRV-positive children were 13-36 months of age (χ(2)  = 22.803, P = 0.000). HRV was detected year round and peaked between September and December. Fifty-three percent of the HRV-positive samples were also positive for other respiratory viruses; respiratory syncytial virus (RSV) was the most common secondary virus. Phylogenetic analysis using the VP4/VP2 region grouped the HRV-positive strains as follows: 101 HRV-A (50.0%), 21 HRV-B (10.4%), and 80 HRV-C (39.6%). HRV-A infections occurred predominantly in spring and autumn, and the peak prevalence of HRV-C was in early winter and late autumn. HRV-B infections were less common in spring (χ(2)  = 31.914, P = 0.000). No significant difference in clinical severity or presentation was found between patients with HRV single infection and HRV co-detections. Furthermore, the clinical characterizations did not differ among the three HRV species. These results suggest that HRV-C is an important viral agent along with HRV-A and HRV-B and that among hospitalized children with acute lower respiratory tract infection in China, the three HRV genotypes have similar clinical characteristics. © 2014 Wiley Periodicals, Inc.

  20. Differential impact of respiratory syncytial virus and parainfluenza virus on the frequency of acute otitis media is explained by lower adaptive and innate immune responses in otitis-prone children.

    Science.gov (United States)

    Verhoeven, David; Xu, Qingfu; Pichichero, Michael E

    2014-08-01

    Acute otitis media (AOM) is a leading cause of bacterial pediatric infections associated with viral upper respiratory infections (URIs). We examined the differential impact of respiratory syncytial virus (RSV) and parainfluenza virus URIs on the frequency of AOM caused by Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi) in stringently defined otitis-prone (sOP) and non-otitis-prone (NOP) children as a potential mechanism to explain increased susceptibility to AOM. Peripheral blood and nasal washes were obtained from sOP and NOP children (n = 309). Colonization events and antiviral responses consisting of total specific immunoglobulin G (IgG) responses, neutralizing antibody responses, and T-cell responses were determined. Isolated neutrophils were infected with varying multiplicities of infection of both viruses, and opsonophagocytosis potential was measured. A significant increase was found in frequency of AOM events caused by Spn and NTHi, with a concurrent RSV infection in sOP children. These results correlated with diminished total RSV-specific IgG, higher viral nasal burdens, and lower IgG neutralizing capacity. The sOP children had diminished T-cell responses to RSV that correlated with lower Toll-like receptor 3/7 transcript and decreased expression of HLA-DR on antigen-presenting cells. RSV interfered with the Spn phagocytic capacity of neutrophils in a dose-dependent manner. Parainfluenza virus infections did not differentially affect AOM events in sOP and NOP children. Lower innate and adaptive immune responses to RSV in sOP children may slow the kinetics of viral clearance from the nasopharynx and allow for viral interference with antibacterial immune responses, thus contributing to increased frequency of AOMs. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Dynamics of human respiratory system mycoflora

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    Anna Biedunkiewicz

    2014-08-01

    Full Text Available The study aimed at determing the prevalence of individual species of fungi in the respiratory systems of women and men, analysis of the dynamics of the fungi in individual sections of the respiratory system as concerns their quantity and identification of phenology of the isolated fungi coupled with an attempt at identifying their possible preferences for appearing during specific seasons of thc year. During 10 years of studies (1989- 1998. 29 species of fungi belonging: Candida, Geolrichum, Saccharomyces, Saccharomycopsis, Schizosaccharomyces, Torulopsis, Trichosporon and Aspergillus were isolated from the ontocenoses of the respiratory systems of patients at the Independent Public Center for Pulmonology and Oncology in Olsztyn. Candida albicans was a clearly dominating fungus. Individual species appeared individually, in twos or threes in a single patient, they were isolated more frequently in the spring and autumn, less frequently during the winter and summer. The largest number of fungi species were isolated from sputum (29 species, bronchoscopic material (23 species and pharyngeal swabs (15 species. Sacchoromycopsis capsularis and Trichosporon beigelii should be treated as new for the respiratory system. Biodiversity of fungi, their numbers and continous fluctuations in frequency indicate that the respiratory system ontocenose offers the optimum conditions for growth and development of the majority of the majority of yeasts - like fungi.

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

    Science.gov (United States)

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

    2015-06-01

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

  3. Evaluation of an intranasal virosomal vaccine against respiratory syncytial virus in mice: effect of TLR2 and NOD2 ligands on induction of systemic and mucosal immune responses.

    Directory of Open Access Journals (Sweden)

    Muhammad Shafique

    Full Text Available INTRODUCTION: RSV infection remains a serious threat to newborns and the elderly. Currently, there is no vaccine available to prevent RSV infection. A mucosal RSV vaccine would be attractive as it could induce mucosal as well as systemic antibodies, capable of protecting both the upper and lower respiratory tract. Previously, we reported on a virosomal RSV vaccine for intramuscular injection with intrinsic adjuvant properties mediated by an incorporated lipophilic Toll-like receptor 2 (TLR2 ligand. However, it has not been investigated whether this virosomal RSV vaccine candidate would be suitable for use in mucosal immunization strategies and if additional incorporation of other innate receptor ligands, like NOD2-ligand, could further enhance the immunogenicity and protective efficacy of the vaccine. OBJECTIVE: To explore if intranasal (IN immunization with a virosomal RSV vaccine, supplemented with TLR2 and/or NOD2-ligands, is an effective strategy to induce RSV-specific immunity. METHODS: We produced RSV-virosomes carrying TLR2 (Pam3CSK4 and/or NOD2 (L18-MDP ligands. We tested the immunopotentiating properties of these virosomes in vitro, using TLR2- and/or NOD2-ligand-responsive murine and human cell lines, and in vivo by assessing induction of protective antibody and cellular responses upon IN immunization of BALB/c mice. RESULTS: Incorporation of Pam3CSK4 and/or L18-MDP potentiates the capacity of virosomes to activate (antigen-presenting cells in vitro, as demonstrated by NF-κB induction. In vivo, incorporation of Pam3CSK4 in virosomes boosted serum IgG antibody responses and mucosal antibody responses after IN immunization. While L18-MDP alone was ineffective, incorporation of L18-MDP in Pam3CSK4-carrying virosomes further boosted mucosal antibody responses. Finally, IN immunization with adjuvanted virosomes, particularly Pam3CSK4/L18-MDP-adjuvanted-virosomes, protected mice against infection with RSV, without priming for enhanced

  4. A recombinant anchorless respiratory syncytial virus (RSV) fusion (F) protein/monophosphoryl lipid A (MPL) vaccine protects against RSV-induced replication and lung pathology.

    Science.gov (United States)

    Blanco, Jorge C G; Boukhvalova, Marina S; Pletneva, Lioubov M; Shirey, Kari Ann; Vogel, Stefanie N

    2014-03-14

    We previously demonstrated that the severe cytokine storm and pathology associated with RSV infection following intramuscular vaccination of cotton rats with FI-RSV Lot 100 could be completely abolished by formulating the vaccine with the mild TLR4 agonist and adjuvant, monophosphoryl lipid A (MPL). Despite this significant improvement, the vaccine failed to blunt viral replication in the lungs. Since MPL is a weak TLR4 agonist, we hypothesized that its adjuvant activity was mediated by modulating the innate immune response of respiratory tract resident macrophages. Therefore, we developed a new vaccine preparation with purified, baculovirus expressed, partially purified, anchorless RSV F protein formulated with synthetic MPL that was administered to cotton rats intranasally, followed by an intradermal boost. This novel formulation and heterologous "prime/boost" route of administration resulted in decreased viral titers compared to that seen in animals vaccinated with F protein alone. Furthermore, animals vaccinated by this route showed no evidence of enhanced lung pathology upon RSV infection. This indicates that MPL acts as an immune modulator that protects the host from vaccine-enhanced pathology, and reduces RSV replication in the lower respiratory tract when administered by a heterologous prime/boost immunization regimen. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Computational Fluid and Particle Dynamics in the Human Respiratory System

    CERN Document Server

    Tu, Jiyuan; Ahmadi, Goodarz

    2013-01-01

    Traditional research methodologies in the human respiratory system have always been challenging due to their invasive nature. Recent advances in medical imaging and computational fluid dynamics (CFD) have accelerated this research. This book compiles and details recent advances in the modelling of the respiratory system for researchers, engineers, scientists, and health practitioners. It breaks down the complexities of this field and provides both students and scientists with an introduction and starting point to the physiology of the respiratory system, fluid dynamics and advanced CFD modeling tools. In addition to a brief introduction to the physics of the respiratory system and an overview of computational methods, the book contains best-practice guidelines for establishing high-quality computational models and simulations. Inspiration for new simulations can be gained through innovative case studies as well as hands-on practice using pre-made computational code. Last but not least, students and researcher...

  6. The performance of Luminex ARIES® Flu A/B & RSV and Cepheid Xpert® Flu/RSV XC for the detection of influenza A, influenza B, and respiratory syncytial virus in prospective patient samples.

    Science.gov (United States)

    McMullen, Phillip; Boonlayangoor, Sue; Charnot-Katsikas, Angella; Beavis, Kathleen G; Tesic, Vera

    2017-10-01

    The demand for rapid, accurate viral testing has increased the number of assays available for the detection of viral pathogens. One of the newest FDA cleared platforms is the Luminex ARIES ® Flu A/B & RSV, which is a fully automated, real-time PCR-based assay used for detection of influenza A, influenza B, and respiratory syncytial virus (RSV). We sought to compare the performance of Luminex ARIES ® Flu A/B & RSV assay to the Cepheid Xpert ® Flu/RSV XC assay for rapid Flu and RSV testing. A series of consecutive nasopharyngeal specimens received in the clinical microbiology laboratory during peak influenza season at a major academic center in Chicago, IL, were prospectively tested, using both the ARIES ® Flu A/B & RSV and Xpert ® Flu/RSV XC assays, side by side. Discrepant results were tested on the BioFire FilmArray ® Respiratory Panel for resolution. A total of 143 consecutive nasopharyngeal specimens, obtained from patients ranging from six months to ninety-three years in age were received between January 1st, 2017 and March 21st, 2017. There was 96.6% agreement between the two assays for detection influenza A, 100% agreement for detection influenza B and RSV, and 98.9% agreement for negative results. The Xpert ® Flu/RSV XC performed with an average turn-around time of approximately 60min, compared to the ARIES ® Flu A/B & RSV of approximately 120min. Both assays were equally easy to perform, with a similar amount of hands-on technologist time for each platform. Overall, these results indicate that both tests are comparable in terms of result agreement and technical ease-of-use. The Xpert ® Flu/RSV XC assay did produce results with less turn-around-time, approximately 60min quicker than the ARIES ® Flu A/B & RSV. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The pressure gradient in the human respiratory tract

    Directory of Open Access Journals (Sweden)

    Chovancová Michaela

    2014-03-01

    Full Text Available Respiratory airways cause resistance to air flow during inhalation and exhalation. The pressure gradient is necessary to transport the air from the mount (or nose to pulmonary alveoli. The knowledge of pressure gradient (i.e. respiratory airways resistance is also needed to solve the question of aerosol deposition in the human respiratory tract. The obtained data will be used as boundary conditions for CFD simulations of aerosol transport. Understanding of aerosol transport in the human lungs can help us to determine the health hazard of harmful particles. On the other hand it can be used to set the conditions for transport of medication to the desirable place. This article deals with the description of the mathematical equations defining the pressure gradient and resistance in the bronchial three and describes the geometry used in the calculation.

  8. CpG in Combination with an Inhibitor of Notch Signaling Suppresses Formalin-Inactivated Respiratory Syncytial Virus-Enhanced Airway Hyperresponsiveness and Inflammation by Inhibiting Th17 Memory Responses and Promoting Tissue-Resident Memory Cells in Lungs.

    Science.gov (United States)

    Zhang, Lei; Li, Hongyong; Hai, Yan; Yin, Wei; Li, Wenjian; Zheng, Boyang; Du, Xiaomin; Li, Na; Zhang, Zhengzheng; Deng, Yuqing; Zeng, Ruihong; Wei, Lin

    2017-05-15

    Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine-enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross talk between TLR and Notch signaling pathways results in fine-tuning of TLR-triggered innate inflammatory responses. We evaluated the impact of TLR and Notch signaling on ERD in a murine model by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling during FI-RSV immunization. Activation with CpG or deficiency of MyD88-dependent TLR signaling did not alleviate airway inflammation in FI-RSV-immunized mice. Activation or inhibition of Notch signaling with Dll4, one of the Notch ligands, or L685,458 did not suppress FI-RSV-enhanced airway inflammation either. However, the CpG together with L685,458 markedly inhibited FI-RSV-enhanced airway hyperresponsiveness, weight loss, and lung inflammation. Interestingly, CpG plus L685,458 completely inhibited FI-RSV-associated Th17 and Th17-associated proinflammatory chemokine responses in lungs following RSV challenge but not Th1 or Th2, memory responses. In addition, FI-RSV plus CpG plus L685,458 promoted protective CD8 + lung tissue-resident memory (TRM) cells. These results indicate that activation of TLR signaling combined with inhibition of Notch signaling prevent FI-RSV ERD, and the mechanism appears to involve suppressing proinflammatory Th17 memory responses and promoting protective TRM in lungs. IMPORTANCE RSV is the most important cause of lower respiratory tract infections in infants. The FI-RSV-enhanced respiratory disease (ERD) is a major impediment to the development of a safe and

  9. Global Considerations in Human Immunodeficiency Virus-Associated Respiratory Disease.

    Science.gov (United States)

    Rylance, Jamie; Meghji, Jamilah; Miller, Robert F; Ferrand, Rashida A

    2016-04-01

    Respiratory tract infection, particularly tuberculosis, is a major cause of mortality among human immunodeficiency virus (HIV)-infected individuals. Antiretroviral therapy (ART) has resulted in a dramatic increase in survival, although coverage of HIV treatment remains low in many parts of the world. There is a concurrent growing burden of chronic noninfectious respiratory disease as a result of increased survival. Many risk factors associated with the development of respiratory disease, such as cigarette smoking and intravenous drug use, are overrepresented among people living with HIV. In addition, there is emerging evidence that HIV infection may directly cause or accelerate the course of chronic lung disease. This review summarizes the clinical spectrum and epidemiology of respiratory tract infections and noninfectious pulmonary pathologies, and factors that explain the global variation in HIV-associated respiratory disease. The potential for enhancing diagnoses of noninfective chronic conditions through the use of clinical algorithms is discussed. We also consider issues in assessment and management of HIV-related respiratory disease in view of the increasing global scale up of ART. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. Respiratory

    Science.gov (United States)

    The words "respiratory" and "respiration" refer to the lungs and breathing. ... Boron WF. Organization of the respiratory system. In: Boron WF, Boulpaep EL, eds. Medical Physiology . 3rd ed. Philadelphia, PA: Elsevier; 2017:chap 26.

  11. Tetratrichomonads from the oral cavity and respiratory tract of humans

    Czech Academy of Sciences Publication Activity Database

    Kutišová, K.; Kulda, J.; Čepička, I.; Flegr, J.; Koudela, Břetislav; Teras, J.; Tachezy, J.

    2005-01-01

    Roč. 131, č. 1 (2005), s. 1-11 ISSN 0031-1820 Grant - others:Grantová agentura Karlovy univerzity v Praze(CZ) 264/1999 Institutional research plan: CEZ:AV0Z60220518 Keywords : Tetratrichomonas spp. * human respiratory tract * oral cavity Subject RIV: EE - Microbiology, Virology Impact factor: 1.703, year: 2005

  12. 3-D Model of the Human Respiratory System

    Science.gov (United States)

    The U.S. EPA’s Office of Research and Development (ORD) has developed a 3-D computational fluid dynamics (CFD) model of the human respiratory system that allows for the simulation of particulate based contaminant deposition and clearance, while being adaptable for age, ethnicity,...

  13. Computational 3-D Model of the Human Respiratory System

    Science.gov (United States)

    We are developing a comprehensive, morphologically-realistic computational model of the human respiratory system that can be used to study the inhalation, deposition, and clearance of contaminants, while being adaptable for age, race, gender, and health/disease status. The model ...

  14. Characterization of novel human respiratory viruses

    NARCIS (Netherlands)

    Dijkman, R.

    2011-01-01

    Wereldwijd komen vier humane coronavirussen (HCoVs) voor, waaronder NL63 en 229E. NL63 werd in 2004 ontdekt in het AMC en veroorzaakt de kinderziekte pseudokroep; 229E is een verkoudheidsvirus. Waarschijnlijk veroorzaken beide virussen vergelijkbare symptomen bij volwassenen. Er is weinig bekend

  15. Respiratory Syncytial Virus Fusion Protein-Induced Toll-Like Receptor 4 (TLR4) Signaling Is Inhibited by the TLR4 Antagonists Rhodobacter sphaeroides Lipopolysaccharide and Eritoran (E5564) and Requires Direct Interaction with MD-2

    Science.gov (United States)

    Rallabhandi, Prasad; Phillips, Rachel L.; Boukhvalova, Marina S.; Pletneva, Lioubov M.; Shirey, Kari Ann; Gioannini, Theresa L.; Weiss, Jerrold P.; Chow, Jesse C.; Hawkins, Lynn D.; Vogel, Stefanie N.; Blanco, Jorge C. G.

    2012-01-01

    ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of infant mortality worldwide. Toll-like receptor 4 (TLR4), a signaling receptor for structurally diverse microbe-associated molecular patterns, is activated by the RSV fusion (F) protein and by bacterial lipopolysaccharide (LPS) in a CD14-dependent manner. TLR4 signaling by LPS also requires the presence of an additional protein, MD-2. Thus, it is possible that F protein-mediated TLR4 activation relies on MD-2 as well, although this hypothesis has not been formally tested. LPS-free RSV F protein was found to activate NF-κB in HEK293T transfectants that express wild-type (WT) TLR4 and CD14, but only when MD-2 was coexpressed. These findings were confirmed by measuring F-protein-induced interleukin 1β (IL-1β) mRNA in WT versus MD-2−/− macrophages, where MD-2−/− macrophages failed to show IL-1β expression upon F-protein treatment, in contrast to the WT. Both Rhodobacter sphaeroides LPS and synthetic E5564 (eritoran), LPS antagonists that inhibit TLR4 signaling by binding a hydrophobic pocket in MD-2, significantly reduced RSV F-protein-mediated TLR4 activity in HEK293T-TLR4–CD14–MD-2 transfectants in a dose-dependent manner, while TLR4-independent NF-κB activation by tumor necrosis factor alpha (TNF-α) was unaffected. In vitro coimmunoprecipitation studies confirmed a physical interaction between native RSV F protein and MD-2. Further, we demonstrated that the N-terminal domain of the F1 segment of RSV F protein interacts with MD-2. These data provide new insights into the importance of MD-2 in RSV F-protein-mediated TLR4 activation. Thus, targeting the interaction between MD-2 and RSV F protein may potentially lead to novel therapeutic approaches to help control RSV-induced inflammation and pathology. PMID:22872782

  16. Anti-respiratory syncytial virus (RSV) G monoclonal antibodies reduce lung inflammation and viral lung titers when delivered therapeutically in a BALB/c mouse model.

    Science.gov (United States)

    Caidi, Hayat; Miao, Congrong; Thornburg, Natalie J; Tripp, Ralph A; Anderson, Larry J; Haynes, Lia M

    2018-06-01

    RSV continues to be a high priority for vaccine and antiviral drug development. Unfortunately, no safe and effective RSV vaccine is available and treatment options are limited. Over the past decade, several studies have focused on the role of RSV G protein on viral entry, viral neutralization, and RSV-mediated pathology. Anti-G murine monoclonal antibody (mAb) 131-2G treatment has been previously shown to reduce weight loss, bronchoalveolar lavage (BAL) cell number, airway reactivity, and Th2-type cytokine production in RSV-infected mice more rapidly than a commercial humanized monoclonal antibody (mAb) against RSV F protein (Palivizumab). In this study, we have tested two human anti-RSV G mAbs, 2B11 and 3D3, by both prophylactic and therapeutic treatment for RSV in the BALB/c mouse model. Both anti-G mAbs reduced viral load, leukocyte infiltration and IFN-γ and IL-4 expression in cell-free BAL supernatants emphasizing the potential of anti-G mAbs as anti-inflammatory and antiviral strategies. Published by Elsevier B.V.

  17. Human torso phantom for imaging of heart with realistic modes of cardiac and respiratory motion

    Science.gov (United States)

    Boutchko, Rostyslav; Balakrishnan, Karthikayan; Gullberg, Grant T; O& #x27; Neil, James P

    2013-09-17

    A human torso phantom and its construction, wherein the phantom mimics respiratory and cardiac cycles in a human allowing acquisition of medical imaging data under conditions simulating patient cardiac and respiratory motion.

  18. Motavizumab, A Neutralizing Anti-Respiratory Syncytial Virus (Rsv Monoclonal Antibody Significantly Modifies The Local And Systemic Cytokine Responses Induced By Rsv In The Mouse Model

    Directory of Open Access Journals (Sweden)

    Jafri Hasan S

    2007-10-01

    Full Text Available Abstract Motavizumab (MEDI-524 is a monoclonal antibody with enhanced neutralizing activity against RSV. In mice, motavizumab suppressed RSV replication which resulted in significant reduction of clinical parameters of disease severity. We evaluated the effect of motavizumab on the local and systemic immune response induced by RSV in the mouse model. Balb/c mice were intranasally inoculated with 106.5 PFU RSV A2 or medium. Motavizumab was given once intraperitoneally (1.25 mg/mouse as prophylaxis, 24 h before virus inoculation. Bronchoalveolar lavage (BAL and serum samples were obtained at days 1, 5 (acute and 28 (long-term post inoculation and analyzed with a multiplex assay (Beadlyte Upstate, NY for simultaneous quantitation of 18 cytokines: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, KC (similar to human IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-17, TNF-α, MCP-1, RANTES, IFN-γ and GM-CSF. Overall, cytokine concentrations were lower in serum than in BAL samples. By day 28, only KC was detected in BAL specimens at low concentrations in all groups. Administration of motavizumab significantly reduced (p

  19. Antigenic and genetic variability of human metapneumoviruses

    NARCIS (Netherlands)

    S. Herfst (Sander); L. Sprong; P.A. Cane; E. Forleo-Neto; A.D.M.E. Osterhaus (Albert); R.A.M. Fouchier (Ron); R.L. de Swart (Rik); B.G. van den Hoogen (Bernadette)

    2004-01-01

    textabstractHuman metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups on the basis of genetic or antigenic differences or both. For

  20. Human bocavirus in children with acute respiratory infections in Vietnam.

    Science.gov (United States)

    Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2014-06-01

    Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. © 2013 Wiley Periodicals, Inc.

  1. Human coronavirus and severe acute respiratory infection in Southern Brazil.

    Science.gov (United States)

    Trombetta, Hygor; Faggion, Heloisa Z; Leotte, Jaqueline; Nogueira, Meri B; Vidal, Luine R R; Raboni, Sonia M

    2016-05-01

    Human coronaviruses (HCoVs) are an important cause of respiratory tract infection and are responsible for causing the common cold in the general population. Thus, adequate surveillance of HCoV is essential. This study aimed to analyze the impact of HCoV infections and their relation to severe acute respiratory infection (SARI) in a hospitalized population in Southern Brazil. A cross-sectional study was conducted at a tertiary care hospital, and assessed inpatients under investigation for SARI by the hospital epidemiology department, and all patients who had nasopharyngeal aspirates collected from January 2012 to December 2013 to detect respiratory viruses (RVs). Viral infection was detected by multiplex reverse transcriptase polymerase chain reaction (RT-PCR), with primers specific to the subtypes HCoV-229E/NL63 and OC43/HKU1. The overall positivity rate was 58.8% (444/755), and HCoVs were detected in 7.6% (n = 34) of positive samples. Children below two years of age were most frequently affected (62%). Comorbidities were more likely to be associated with HCoVs than with other RVs. Immunosuppression was an independent risk factor for HCoV infection (OR = 3.5, 95% CI 1.6-7.6). Dyspnea was less frequently associated with HCoV infection (p infected with HCoV (9%) died from respiratory infection. HCoVs are important respiratory pathogens, especially in hospitalized children under 2 years of age and in immunosuppressed patients. They may account for a small proportion of SARI diagnoses, increased need for mechanical ventilation, intensive care unit admission, and death.

  2. Clinical patterns and seasonal trends in respiratory syncytial virus hospitalizations in São Paulo, Brazil Padrões clínicos e sazonalidade das hospitalizações causadas pelo vírus respiratório sincicial em São Paulo, Brasil

    Directory of Open Access Journals (Sweden)

    Sandra E. VIEIRA

    2001-06-01

    Full Text Available The respiratory viruses are recognized as the most frequent lower respiratory tract pathogens for infants and young children in developed countries but less is known for developing populations. The authors conducted a prospective study to evaluate the occurrence, clinical patterns, and seasonal trends of viral infections among hospitalized children with lower respiratory tract disease (Group A. The presence of respiratory viruses in children's nasopharyngeal was assessed at admission in a pediatric ward. Cell cultures and immunofluorescence assays were used for viral identification. Complementary tests included blood and pleural cultures conducted for bacterial investigation. Clinical data and radiological exams were recorded at admission and throughout the hospitalization period. To better evaluate the results, a non- respiratory group of patients (Group B was also constituted for comparison. Starting in February 1995, during a period of 18 months, 414 children were included- 239 in Group A and 175 in Group B. In Group A, 111 children (46.4% had 114 viruses detected while only 5 children (2.9% presented viruses in Group B. Respiratory Syncytial Virus was detected in 100 children from Group A (41.8%, Adenovirus in 11 (4.6%, Influenza A virus in 2 (0.8%, and Parainfluenza virus in one child (0.4%. In Group A, aerobic bacteria were found in 14 cases (5.8%. Respiratory Syncytial Virus was associated to other viruses and/or bacteria in six cases. There were two seasonal trends for Respiratory Syncytial Virus cases, which peaked in May and June. All children affected by the virus were younger than 3 years of age, mostly less than one year old. Episodic diffuse bronchial commitment and/or focal alveolar condensation were the clinical patterns more often associated to Respiratory Syncytial Virus cases. All children from Group A survived. In conclusion, it was observed that Respiratory Syncytial Virus was the most frequent pathogen found in hospitalized

  3. Respiratory compensation to a primary metabolic alkalosis in humans.

    Science.gov (United States)

    Feldman, Mark; Alvarez, Naiara M; Trevino, Michael; Weinstein, Gary L

    2012-11-01

    There is limited and disparate information about the extent of the respiratory compensation (hypoventilation) that occurs in response to a primary metabolic alkalosis in humans. Our aim was to examine the influence of the plasma bicarbonate concentration, the plasma base excess, and the arterial pH on the arterial carbon dioxide tension in 52 adult patients with primary metabolic alkalosis, mostly due to diuretic use or vomiting. Linear regression analysis was used to correlate degrees of alkalosis with arterial carbon dioxide tensions. In this alkalotic cohort, whose arterial plasma bicarbonate averaged 31.6 mEq/l, plasma base excess averaged 7.8 mEq/l, and pH averaged 7.48, both plasma bicarbonate and base excess correlated closely with arterial carbon dioxide tensions (r = 0.97 and 0.96, respectively; p respiratory compensation (hypoventilation) to primary metabolic alkalosis than has been reported in prior smaller studies.

  4. Ozone exposure increases respiratory epithelial permeability in humans

    International Nuclear Information System (INIS)

    Kehrl, H.R.; Vincent, L.M.; Kowalsky, R.J.; Horstman, D.H.; O'Neil, J.J.; McCartney, W.H.; Bromberg, P.A.

    1987-01-01

    Ozone is a respiratory irritant that has been shown to cause an increase in the permeability of the respiratory epithelium in animals. We used inhaled aerosolized /sup 99m/Tc-labeled diethylene triamine pentacetic acid (/sup 99m/Tc-DTPA) to investigate whether human respiratory epithelial permeability is similarly affected by exposure to ozone. In a randomized, crossover double-blinded study, 8 healthy, nonsmoking young men were exposed for 2 h to purified air and 0.4 ppm ozone while performing intermittent high intensity treadmill exercise (minute ventilation = 66.8 L/min). SRaw and FVC were measured before and at the end of exposures. Seventy-five minutes after the exposures, the pulmonary clearance of /sup 99m/Tc-DTPA was measured by sequential posterior lung imaging with a computer-assisted gamma camera. Ozone exposure caused respiratory symptoms in all 8 subjects and was associated with a 14 +/- 2.8% (mean +/- SEM) decrement in FVC (p less than 0.001) and a 71 +/- 22% increase in SRaw (p = 0.04). Compared with the air exposure day, 7 of the 8 subjects showed increased /sup 99m/Tc-DTPA clearance after the ozone exposure, with the mean value increasing from 0.59 +/- 0.08 to 1.75 +/- 0.43%/min (p = 0.03). These data show that ozone exposure sufficient to produce decrements in the pulmonary function of human subjects also causes an increase in /sup 99m/Tc-DTPA clearance

  5. Usefulness of Ct value in acute respiratory infections caused by respiratory syncytial virus A and B and influenza virus A (H1N1)pdm09, A (H3N2) and B.

    Science.gov (United States)

    Reina, Jordi; Morales, Carmen; Busquets, María; Norte, Cristina

    2017-06-07

    Acute respiratory infections of viral cause are very frequent entities. The difficulty in evaluating the detection of a virus in these entities could be solved by determining the viral load. A prospective study on the mean Ct value (cycle threshold value) detected against RSV-A, RSV-B and influenza A (H1N1)pdm09, A (H3N2) and B viruses in patients of different origin and age was performed. Detection was performed using a commercial molecular amplification (RT-PCR) technique. Different mean Ct values were detected for each virus. In RSV infections, no differences were observed between those caused by RSV-A or RSV-B in children. Depending on the patient's age, the only statistical significance was observed in those included in the 0-4 month groups for RSV-A and this group and the 5-12 months group for RSV-B (higher values). A lower viral load was detected in adult patients than in paediatric patients. In influenza infections, no statistical significance was observed in the mean values detected in patients from the Red Centinela («sentinel network», a Spanish network of doctors aimed at research and surveillance of diseases), those diagnosed in the adult emergency room or in hospital admissions. In the adult patients admitted to the ICU, only a slightly lower mean value was observed in those infected with influenza A (H1N1)pdm09, but without statistical significance. There were no patients admitted to the ICU with influenza B infection. The detection of viral load could be a good tool for the evaluation, monitoring and prognosis of acute viral respiratory infections. With the exception of those caused by RSV, no significant differences were observed in influenza infections except in younger paediatric patients. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. Comparative studies on virus detection in acute respiratory diseases in humans by means of RIA and cultivation

    International Nuclear Information System (INIS)

    Ehrlicher, L.

    1982-01-01

    In winter 1981, 146 patients with an acute respiratory infection were examined. Nasopharyngeal specimens were obtained by intranasal catheter. Comparative investigations were performed by cultivation in tissue culture and by a four-layer radioimmunoassay. In the radioimmunoassay, polystyrene beads were used as the solid phase, ginea pig antivirus immunoglobulins as the captive antibodies, rabbit anti-virus immunoglobulins as the secondary antibodies and 125 I-labelled sheep anti-rabbit immunoglobulins were used as the indicator antibodies. The radioimmunoassay was developed for the detection of adenovirus, respiratory syncytial virus, influenza A and B virus and parainfluenza type 1, type 2 and type 3 virus. Tissue culture seems to be more sensitive for detection of adenovirus and influenza A virus, though some infections with influenza A virus could only be diagnosed by the radioimmunoassay. In other cases (respiratory syncytial virus, influenza B virus) antigen detection by radioimmunoassay is more efficient. Presently the combination of both antigen-detection-systems still is the optimal diagnostic procedure for detecting virus infections of the respiratory tract. (orig./MG) [de

  7. 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

    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......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...

  8. Respiratory Viruses in Febrile Neutropenic Patients with Respiratory Symptoms

    Directory of Open Access Journals (Sweden)

    Mohsen Meidani

    2018-01-01

    Full Text Available Background: Respiratory infections are a frequent cause of fever in neutropenic patients, whereas respiratory viral infections are not frequently considered as a diagnosis, which causes high morbidity and mortality in these patients. Materials and Methods: This prospective study was performed on 36 patients with neutropenia who admitted to hospital were eligible for inclusion with fever (single temperature of >38.3°C or a sustained temperature of >38°C for more than 1 h, upper and lower respiratory symptoms. Sampling was performed from the throat of the patient by the sterile swab. All materials were analyzed by quantitative real-time multiplex polymerase chain reaction covering the following viruses; influenza, parainfluenza virus (PIV, rhinovirus (RV, human metapneumovirus, and respiratory syncytial virus (RSV. Results: RV was the most frequently detected virus and then RSV was the most. PIV was not present in any of the tested samples. Furthermore, no substantial differences in the distribution of specific viral species were observed based on age, sex, neutropenia duration, hematological disorder, and respiratory tract symptoms and signs (P > 0.05. Conclusion: Our prospective study supports the hypothesis that respiratory viruses play an important role in the development of neutropenic fever, and thus has the potential to individualize infection treatment and to reduce the extensive use of antibiotics in immunocompromised patients with neutropenia.

  9. Diversity of aging of the immune system classified in the cotton rat (Sigmodon hispidus) model of human infectious diseases.

    NARCIS (Netherlands)

    Guichelaar, Teun; van Erp, Elisabeth A; Hoeboer, Jeroen; Smits, Noortje A M; van Els, Cécile A C M; Pieren, Daan K J; Luytjes, Willem

    2018-01-01

    Susceptibility and declined resistance to human pathogens like respiratory syncytial virus (RSV) at old age is well represented in the cotton rat (Sigmodon hispidus). Despite providing a preferred model of human infectious diseases, little is known about aging of its adaptive immune system. We aimed

  10. A Novel Parametric Model For The Human Respiratory System

    Directory of Open Access Journals (Sweden)

    Clara Mihaela IONESCU

    2003-12-01

    Full Text Available The purpose of this work is to present some recent results in an ongoing research project between Ghent University and Chess Medical Technology Company Belgium. The overall aim of the project is to provide a fast method for identification of the human respiratory system in order to allow for an instantaneously diagnosis of the patient by the medical staff. A novel parametric model of the human respiratory system as well as the obtained experimental results is presented in this paper. A prototype apparatus developed by the company, based on the forced oscillation technique is used to record experimental data from 4 patients in this paper. Signal processing is based on spectral analysis and is followed by the parametric identification of a non-linear mechanistic model. The parametric model is equivalent to the structure of a simple electrical RLC-circuit, containing a non-linear capacitor. These parameters have a useful and easy-to-interpret physical meaning for the medical staff members.

  11. Velocity profiles in idealized model of human respiratory tract

    Science.gov (United States)

    Elcner, J.; Jedelsky, J.; Lizal, F.; Jicha, M.

    2013-04-01

    This article deals with numerical simulation focused on velocity profiles in idealized model of human upper airways during steady inspiration. Three r gimes of breathing were investigated: Resting condition, Deep breathing and Light activity which correspond to most common regimes used for experiments and simulations. Calculation was validated with experimental data given by Phase Doppler Anemometry performed on the model with same geometry. This comparison was made in multiple points which form one cross-section in trachea near first bifurcation of bronchial tree. Development of velocity profile in trachea during steady inspiration was discussed with respect for common phenomenon formed in trachea and for future research of transport of aerosol particles in human respiratory tract.

  12. Velocity profiles in idealized model of human respiratory tract

    Directory of Open Access Journals (Sweden)

    Jicha M.

    2013-04-01

    Full Text Available This article deals with numerical simulation focused on velocity profiles in idealized model of human upper airways during steady inspiration. Three r gimes of breathing were investigated: Resting condition, Deep breathing and Light activity which correspond to most common regimes used for experiments and simulations. Calculation was validated with experimental data given by Phase Doppler Anemometry performed on the model with same geometry. This comparison was made in multiple points which form one cross-section in trachea near first bifurcation of bronchial tree. Development of velocity profile in trachea during steady inspiration was discussed with respect for common phenomenon formed in trachea and for future research of transport of aerosol particles in human respiratory tract.

  13. Do pollution and climate influence respiratory tract infections in children?

    Directory of Open Access Journals (Sweden)

    Saulo Duarte Passos

    2014-06-01

    Full Text Available To review if pollution and climate changes can influence respiratory tract infections in children. Data source: articles published on the subject in PubMed, SciELO, Bireme, EBSCO and UpTodate were reviewed. The following inclusion criteria were considered: scientific papers between 2002 and 2012, study design, the pediatric population, reference documents such as the CETESB and World Health Organization Summary of the data: We analyzed research that correlated respiratory viruses and climate and/or pollution changes. Respiratory syncytial virus has been the virus related most to changes in climate and humidity. Other "old and new" respiratory viruses such as Human Bocavirus, Metapneumovirus, Parechovirus and Parainfuenza would need to be investigated owing to their clinical importance. Although much has been studied with regard to the relationship between climate change and public health, specific studies about its influence on children's health remain scarce.

  14. Interaction of Mycobacterium tuberculosis with human respiratory mucosa.

    Science.gov (United States)

    Middleton, A M; Chadwick, M V; Nicholson, A G; Dewar, A; Groger, R K; Brown, E J; Ratliff, T L; Wilson, R

    2002-01-01

    Endobronchial infection is associated with pulmonary tuberculosis in the majority of cases. We have investigated the adherence of Mycobacterium tuberculosis to the human respiratory mucosa. Organ cultures constructed with human tissue were infected with M. tuberculosis in the presence or absence of mycobacterial fibronectin attachment cell surface proteins and examined by scanning electron microscopy. M. tuberculosis adhered mainly to extracellular matrix (ECM) in areas of mucosal damage, but not to ciliated mucosa, intact extruded cells, basement membrane or collagen fibres. Bacteria also adhered to fibrous but not globular mucus and occasionally to healthy unciliated mucosa, open tight junctions and to extruded cells that had degenerated, exposing their contents. There was a significant reduction (pprotein (FAP) and M. bovis antigen 85B protein, in a concentration dependent manner. The combined effect of FAP and antigen 85B protein was significantly greater than either protein alone. Bacterial adherence to fibrous mucus was not influenced by fibronectin. We conclude that M. tuberculosis adheres to ECM in areas of mucosal damage at least in part via FAP and antigen 85B protein.

  15. Minocycline affects human neutrophil respiratory burst and transendothelial migration.

    Science.gov (United States)

    Parenti, Astrid; Indorato, Boris; Paccosi, Sara

    2017-02-01

    This study aimed at investigating the in vitro activity of minocycline and doxycycline on human polymorphonuclear (h-PMN) cell function. h-PMNs were isolated from whole venous blood of healthy subjects; PMN oxidative burst was measured by monitoring ROS-induced oxidation of luminol and transendothelial migration was studied by measuring PMN migration through a monolayer of human umbilical vein endothelial cells. Differences between multiple groups were determined by ANOVA followed by Tukey's multiple comparison test; Student's t test for unpaired data for two groups. Minocycline (1-300 µM) concentration dependently and significantly inhibited oxidative burst of h-PMNs stimulated with 100 nM fMLP. Ten micromolar concentrations, which are superimposable to C max following a standard oral dose of minocycline, promoted a 29.8 ± 4 % inhibition of respiratory burst (P minocycline impaired PMN transendothelial migration, with maximal effect at 100 µM (42.5 ± 7 %, inhibition, n = 5, P minocycline exerted on innate immune h-PMN cell function.

  16. Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy

    Directory of Open Access Journals (Sweden)

    Eliana C.A. Benites

    2014-07-01

    Full Text Available OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc and University Hospital (HU, Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland, and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta for detection of influenza virus (H1N1, B, rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ2 or Fisher's exact test. RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3% was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%, respiratory syncytial virus AB (8.7%, and coronavirus (6.8%. Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7 were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs.

  17. Characterization of human coronavirus etiology in Chinese adults with acute upper respiratory tract infection by real-time RT-PCR assays.

    Directory of Open Access Journals (Sweden)

    Roujian Lu

    Full Text Available BACKGROUND: In addition to SARS associated coronaviruses, 4 non-SARS related human coronaviruses (HCoVs are recognized as common respiratory pathogens. The etiology and clinical impact of HCoVs in Chinese adults with acute upper respiratory tract infection (URTI needs to be characterized systematically by molecular detection with excellent sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we detected 4 non-SARS related HCoV species by real-time RT-PCR in 981 nasopharyngeal swabs collected from March 2009 to February 2011. All specimens were also tested for the presence of other common respiratory viruses and newly identified viruses, human metapneumovirus (hMPV and human bocavirus (HBoV. 157 of the 981 (16.0% nasopharyngeal swabs were positive for HCoVs. The species detected were 229E (96 cases, 9.8%, OC43 (42 cases, 4.3%, HKU1 (16 cases, 1.6% and NL63 (11 cases, 1.1%. HCoV-229E was circulated in 21 of the 24 months of surveillance. The detection rates for both OC43 and NL63 were showed significantly year-to-year variation between 2009/10 and 2010/11, respectively (P<0.001 and P = 0.003, and there was a higher detection frequency of HKU1 in patients aged over 60 years (P = 0.03. 48 of 157(30.57% HCoV positive patients were co-infected. Undifferentiated human rhinoviruses and influenza (Flu A were the most common viruses detected (more than 35% in HCoV co-infections. Respiratory syncytial virus (RSV, human parainfluenza virus (PIV and HBoV were detected in very low rate (less than 1% among adult patients with URTI. CONCLUSIONS/SIGNIFICANCE: All 4 non-SARS-associated HCoVs were more frequently detected by real-time RT-PCR assay in adults with URTI in Beijing and HCoV-229E led to the most prevalent infection. Our study also suggested that all non-SARS-associated HCoVs contribute significantly to URTI in adult patients in China.

  18. Mitochondrial respiratory efficiency is positively correlated with human sperm motility.

    Science.gov (United States)

    Ferramosca, Alessandra; Provenzano, Sara Pinto; Coppola, Lamberto; Zara, Vincenzo

    2012-04-01

    To correlate sperm mitochondrial respiratory efficiency with variations in sperm motility and with sperm morphologic anomalies. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption carried out in hypotonically-treated sperm cells. A possible relationship among sperm mitochondrial respiratory efficiency, sperm motility, and morphologic anomalies was investigated. Mitochondrial respiratory efficiency was positively correlated with sperm motility and negatively correlated with the percentage of immotile spermatozoa. Moreover, midpiece defects impaired mitochondrial functionality. Our data indicate that an increase in sperm motility requires a parallel increase in mitochondrial respiratory capacity, thereby supporting the fundamental role played by mitochondrial oxidative phosphorylation in sperm motility of normozoospermic subjects. These results are of physiopathological relevance because they suggest that disturbances of sperm mitochondrial function and of energy production could be responsible for asthenozoospermia. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Solution of human respiratory tract model for chronic inhalation intake

    International Nuclear Information System (INIS)

    Nadar, Minal Y.; Singh, I.S.; Rao, D.D.; Pradeepkumar, K.S.

    2014-01-01

    For the radiation workers of fuel reprocessing and fuel fabrication plants, inhalation is one of the major routes of intake of internal contamination. In case of routine monitoring which would result in lung activity above detection limit, it is assumed that intake has occurred at the midpoint of monitoring interval so that underestimation introduced by the unknown time of intake is less than a factor of three. In the plants, chronic intakes of 239 Pu are possible if low levels of 239 Pu activities remain undetected. In ICRP-78, the retention values are given as a function of time for continuous chronic inhalation of 239 Pu at 1.71 Bq/day that would result in Committed Effective Dose (CED) of 20 mSv. Retention values (R) are not given for inhalation intake at any other rate. Therefore, Human Respiratory Tract Model (HRTM) is solved for continuous chronic inhalation at 1 Bq/day rate for type M compounds of 239 Pu to estimate R as a function of time. These values will be useful in estimating intake from lung activity measurements in case of chronic intakes

  20. Lower respiratory tract infection caused by respiratory syncytial virus in infants: the role played by specific antibodies Infecção por virus sincicial respiratório: o papel dos anticorpos séricos específicos

    Directory of Open Access Journals (Sweden)

    Sandra E. Vieira

    2007-01-01

    Full Text Available INTRODUCTION: Respiratory syncytial virus (RSV is a major etiological agent of lower respiratory tract infection in infants. Genotypes of this virus and the role of the infants' serum antibodies have yet to be fully clarified. This knowledge is important for the development of effective therapeutic and prophylactic measures. OBJECTIVES: To evaluate the types and genotypes of RSV causing respiratory tract infection in infants, to analyze the association of subtype-specific serum antibodies with the occurrence of infection and to evaluate the presence of subtype-specific antibodies in the infants' mothers and their association with the profile of the childrens' serum antibodies. METHODS: This was a prospective study on infants hospitalized with respiratory infection. Nasopharyngeal secretions were collected for viral investigation using indirect immunofluorescence and viral culture and blood was collected to test for antibodies using the Luminex Multiplex system. RESULTS: 192 infants were evaluated, with 60.9% having RSV (73.5%- A and 20.5% B. Six genotypes of the virus were identified: A5, A2, B3, B5, A7 and B4. The seroprevalence of the subtype-specific serum antibodies was high. The presence and levels of subtype-specific antibodies were similar, irrespective of the presence of infection or the viral type or genotype. The mothers' antibody profiles were similar to their infants'. CONCLUSIONS: Although the prevalence of subtype-specific antibodies was elevated, these antibodies did not provide protection independently of virus type/genotype. The similarity in the profiles of subtype-specific antibodies presented by the mothers and their children was consistent with transplacental passage.INTRODUÇÃO: O vírus sincicial respiratório é um dos principais agentes etiológicos das infecções do aparelho respiratório inferior em lactentes. Os genótipos deste vírus e o papel dos anticorpos séricos ainda não estão esclarecidos. Este

  1. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses.

    Science.gov (United States)

    van Riel, Debby; den Bakker, Michael A; Leijten, Lonneke M E; Chutinimitkul, Salin; Munster, Vincent J; de Wit, Emmie; Rimmelzwaan, Guus F; Fouchier, Ron A M; Osterhaus, Albert D M E; Kuiken, Thijs

    2010-04-01

    Influenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by virus histochemistry of three human and three avian influenza viruses in human nasal septum, conchae, nasopharynx, paranasal sinuses, and larynx. We found that the human influenza viruses-two seasonal influenza viruses and pandemic H1N1 virus-attached abundantly to ciliated epithelial cells and goblet cells throughout the upper respiratory tract. In contrast, the avian influenza viruses, including the highly pathogenic H5N1 virus, attached only rarely to epithelial cells or goblet cells. Both human and avian viruses attached occasionally to cells of the submucosal glands. The pattern of virus attachment was similar among the different sites of the human upper respiratory tract for each virus tested. We conclude that influenza viruses that are transmitted efficiently among humans attach abundantly to human upper respiratory tract, whereas inefficiently transmitted influenza viruses attach rarely. These results suggest that the ability of an influenza virus to attach to human upper respiratory tract is a critical factor for efficient transmission in the human population.

  2. Mobilisation of toxic elements in the human respiratory system

    International Nuclear Information System (INIS)

    Pinheiro, T.; Alves, L.C.; Palhano, M.J.; Bugalho de Almeida, A.

    2001-01-01

    The fate of respired particles in the respiratory system is inferred through the chemical characterisation of individual particles at the tracheal and bronchial mucosas, and the accumulation of toxic elements in lung alveoli and lymph nodes. The particles and tissue elemental distributions were identified and characterised using micro-PIXE elemental mapping of thin frozen sections using the ITN Nuclear Microprobe facility. Significant particle deposits are found at the distal respiratory tract. Al, Si, Ti, V, Cr, Fe, Ni, Cu and Zn are elements detected at these accumulation areas. The elemental distributions in the different cellular environments of lymph nodes vary. The major compartments for Al, Si, Ti, Fe and Cr are the phagocytic cells and capsule of lymph nodes, while V and Ni are in the cortex and paracortex medullar areas which retain more than 70% of these two elements, suggesting high solubility of the latter in the cellular milieu. The elemental mobilisation from particles or deposits to surrounding tissues at the respiratory ducts evidences patterns of diffusion and removal that are different than those for elements in the respiratory tract. Mobilisation of elements such as V, Cr and Ni is more relevant at alveoli areas where gaseous exchange takes place. The apparent high solubility of V and Ni in the respiratory tract tissue points towards a deviation of the lymphatic system filtering efficiency for these elements when compared to others

  3. Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses

    NARCIS (Netherlands)

    D.A.J. van Riel (Debby); M.A. den Bakker (Michael); L.M.E. Leijten (Lonneke); S. Chutinimitkul (Salin); V.J. Munster (Vincent); E. de Wit (Emmie); G.F. Rimmelzwaan (Guus); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2010-01-01

    textabstractInfluenza viruses vary markedly in their efficiency of human-to-human transmission. This variation has been speculated to be determined in part by the tropism of influenza virus for the human upper respiratory tract. To study this tropism, we determined the pattern of virus attachment by

  4. Promising approaches for the treatment and prevention of viral respiratory illnesses.

    Science.gov (United States)

    Papadopoulos, Nikolaos G; Megremis, Spyridon; Kitsioulis, Nikolaos A; Vangelatou, Olympia; West, Peter; Xepapadaki, Paraskevi

    2017-10-01

    Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Metagenomic analysis of viral diversity in respiratory samples from patients with respiratory tract infections in Kuwait.

    Science.gov (United States)

    Madi, Nada; Al-Nakib, Widad; Mustafa, Abu Salim; Habibi, Nazima

    2018-03-01

    A metagenomic approach based on target independent next-generation sequencing has become a known method for the detection of both known and novel viruses in clinical samples. This study aimed to use the metagenomic sequencing approach to characterize the viral diversity in respiratory samples from patients with respiratory tract infections. We have investigated 86 respiratory samples received from various hospitals in Kuwait between 2015 and 2016 for the diagnosis of respiratory tract infections. A metagenomic approach using the next-generation sequencer to characterize viruses was used. According to the metagenomic analysis, an average of 145, 019 reads were identified, and 2% of these reads were of viral origin. Also, metagenomic analysis of the viral sequences revealed many known respiratory viruses, which were detected in 30.2% of the clinical samples. Also, sequences of non-respiratory viruses were detected in 14% of the clinical samples, while sequences of non-human viruses were detected in 55.8% of the clinical samples. The average genome coverage of the viruses was 12% with the highest genome coverage of 99.2% for respiratory syncytial virus, and the lowest was 1% for torque teno midi virus 2. Our results showed 47.7% agreement between multiplex Real-Time PCR and metagenomics sequencing in the detection of respiratory viruses in the clinical samples. Though there are some difficulties in using this method to clinical samples such as specimen quality, these observations are indicative of the promising utility of the metagenomic sequencing approach for the identification of respiratory viruses in patients with respiratory tract infections. © 2017 Wiley Periodicals, Inc.

  6. The effects of carbon monoxide on respiratory chemoreflexes in humans

    International Nuclear Information System (INIS)

    Vesely, A.E.; Somogyi, R.B.; Sasano, Hiroshi; Sasano, Nobuko; Fisher, J.A.; Duffin, James

    2004-01-01

    As protection against low-oxygen and high-carbon-dioxide environments, the respiratory chemoreceptors reflexly increase breathing. Since CO is also frequently present in such environments, it is important to know whether CO affects the respiratory chemoreflexes responsiveness. Although the peripheral chemoreceptors fail to detect hypoxia produced by CO poisoning, whether CO affects the respiratory chemoreflex responsiveness to carbon dioxide is unknown. The responsiveness of 10 healthy male volunteers were assessed before and after inhalation of ∼1200 ppm CO in air using two iso-oxic rebreathing tests; hypoxic, to emphasize the peripheral chemoreflex, and hyperoxic, to emphasize the central chemoreflex. Although mean (SEM) COHb values of 10.2 (0.2)% were achieved, no statistically significant effects of CO were observed. The average differences between pre- and post-CO values for ventilation response threshold and sensitivity were -0.5 (0.9) mmHg and 0.8 (0.3) L/min/mmHg, respectively, for hyperoxia, and 0.7 (1.1) mmHg and 1.2 (0.8) L/min/mmHg, respectively, for hypoxia. The 95% confidence intervals for the effect of CO were small. We conclude that environments with low levels of CO do not have a clinically significant effect acutely on either the central or the peripheral chemoreflex responsiveness to carbon dioxide

  7. Detection of 12 respiratory viruses by duplex real time PCR assays in respiratory samples.

    Science.gov (United States)

    Arvia, Rosaria; Corcioli, Fabiana; Ciccone, Nunziata; Della Malva, Nunzia; Azzi, Alberta

    2015-12-01

    Different viruses can be responsible for similar clinical manifestations of respiratory infections. Thus, the etiological diagnosis of respiratory viral diseases requires the detection of a large number of viruses. In this study, 6 duplex real-time PCR assays, using EvaGreen intercalating dye, were developed to detect 12 major viruses responsible for respiratory diseases: influenza A and B viruses, enteroviruses (including enterovirus spp, and rhinovirus spp), respiratory syncytial virus, human metapneumovirus, coronaviruses group I (of which CoV 229E and CoV NL63 are part) and II (including CoV OC43 and CoV HKU1), parainfluenza viruses type 1, 2, 3 and 4, human adenoviruses and human bocaviruses. The 2 target viruses of each duplex reaction were distinguishable by the melting temperatures of their amplicons. The 6 duplex real time PCR assays were applied for diagnostic purpose on 202 respiratory samples from 157 patients. One hundred fifty-seven samples were throat swabs and 45 were bronchoalveolar lavages. The results of the duplex PCR assays were confirmed by comparison with a commercial, validated, assay; in addition, the positive results were confirmed by sequencing. The analytical sensitivity of the duplex PCR assays varied from 10(3) copies/ml to 10(4) copies/ml. For parainfluenza virus 2 only it was 10(5) copies/ml. Seventy clinical samples (35%) from 55 patients (30 children and 25 adults) were positive for 1 or more viruses. In adult patients, influenza A virus was the most frequently detected respiratory virus followed by rhinoviruses. In contrast, respiratory syncytial virus was the most common virus in children, followed by enteroviruses, influenza A virus and coronavirus NL63. The small number of samples/patients does not allow us to draw any epidemiological conclusion. Altogether, the results of this study indicate that the 6 duplex PCR assays described in this study are sensitive, specific and cost-effective. Thus, this assay could be

  8. Respiratory system

    Science.gov (United States)

    Bartlett, R. G., Jr.

    1973-01-01

    The general anatomy and function of the human respiratory system is summarized. Breathing movements, control of breathing, lung volumes and capacities, mechanical relations, and factors relevant to respiratory support and equipment design are discussed.

  9. SRS-A leukotrienes decrease the activity of human respiratory cilia

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, M

    1987-01-01

    We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured...

  10. Hyperthermic-induced hyperventilation and associated respiratory alkalosis in humans.

    Science.gov (United States)

    Abbiss, Chris R; Nosaka, Kazunori; Laursen, Paul B

    2007-05-01

    The purpose of this study was to determine if increased environmental heat leads to hyperthermic-induced hypocapnia and associated alkalosis during prolonged self-paced cycling. Nine male cyclists completed three 100 km stochastic time trials in hot (34 degrees C), neutral (22 degrees C) and cold (10 degrees C) environments. Intermittent measurements of rectal and skin temperature, expired gases, blood pH, PaCO(2), PaO(2), and bicarbonate were made throughout. Rectal temperature increased significantly throughout all trials (P respiratory alkalosis.

  11. Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals

    NARCIS (Netherlands)

    D.A.J. van Riel (Debby); V.J. Munster (Vincent); E. de Wit (Emmie); G.F. Rimmelzwaan (Guus); R.A.M. Fouchier (Ron); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2007-01-01

    textabstractViral attachment to the host cell is critical for tissue and species specificity of virus infections. Recently, pattern of viral attachment (PVA) in human respiratory tract was determined for highly pathogenic avian influenza virus of subtype H5N1. However, PVA of human influenza viruses

  12. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans: present knowledge and future investigations.

    Science.gov (United States)

    Mateika, Jason H; Syed, Ziauddin

    2013-09-15

    This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. Published by Elsevier B.V.

  13. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans; present knowledge and future investigations

    Science.gov (United States)

    Mateika, Jason H.; Syed, Ziauddin

    2013-01-01

    This review examines the role that respiratory plasticity has in the maintenance of breathing stability during sleep in individuals with sleep apnea. The initial portion of the review considers the manner in which repetitive breathing events may be initiated in individuals with sleep apnea. Thereafter, the role that two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of upper airway and respiratory muscle activity, might have in modifying breathing events in humans is examined. In this context, present knowledge regarding the initiation of respiratory plasticity in humans during wakefulness and sleep is addressed. Also, published findings which reveal that exposure to intermittent hypoxia promotes breathing instability, at least in part, because of progressive augmentation of the hypoxic ventilatory response and the absence of long-term facilitation, are considered. Next, future directions are presented and are focused on the manner in which forms of plasticity that stabilize breathing might be promoted while diminishing destabilizing forms, concurrently. These future directions will consider the potential role of circadian rhythms in the promotion of respiratory plasticity and the role of respiratory plasticity in enhancing established treatments for sleep apnea. PMID:23587570

  14. The CD8 T Cell Response to Respiratory Virus Infections.

    Science.gov (United States)

    Schmidt, Megan E; Varga, Steven M

    2018-01-01

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

  15. Equation Discovery for Model Identification in Respiratory Mechanics of the Mechanically Ventilated Human Lung

    Science.gov (United States)

    Ganzert, Steven; Guttmann, Josef; Steinmann, Daniel; Kramer, Stefan

    Lung protective ventilation strategies reduce the risk of ventilator associated lung injury. To develop such strategies, knowledge about mechanical properties of the mechanically ventilated human lung is essential. This study was designed to develop an equation discovery system to identify mathematical models of the respiratory system in time-series data obtained from mechanically ventilated patients. Two techniques were combined: (i) the usage of declarative bias to reduce search space complexity and inherently providing the processing of background knowledge. (ii) A newly developed heuristic for traversing the hypothesis space with a greedy, randomized strategy analogical to the GSAT algorithm. In 96.8% of all runs the applied equation discovery system was capable to detect the well-established equation of motion model of the respiratory system in the provided data. We see the potential of this semi-automatic approach to detect more complex mathematical descriptions of the respiratory system from respiratory data.

  16. Mathematical modelling of a human external respiratory system

    Science.gov (United States)

    1977-01-01

    A closed system of algebraic and common differential equations solved by computer is investigated. It includes equations which describe the activity pattern of the respiratory center, the phrenic nerve, the thrust produced by the diaphragm as a function of the lung volume and discharge frequency of the phrenic nerve, as well as certain relations of the lung stretch receptors and chemoreceptors on various lung and blood characteristics, equations for lung biomechanics, pulmonary blood flow, alveolar gas exchange and capillary blood composition equations to determine various air and blood flow and gas exchange parameters, and various gas mixing and arterial and venous blood composition equations, to determine other blood, air and gas mixing characteristics. Data are presented by means of graphs and tables, and some advantages of this model over others are demonstrated by test results.

  17. Respiratory health in Latin America: number of specialists and human resources training.

    Science.gov (United States)

    Vázquez-García, Juan-Carlos; Salas-Hernández, Jorge; Pérez Padilla, Rogelio; Montes de Oca, María

    2014-01-01

    Latin America is made up of a number of developing countries. Demographic changes are occurring in the close to 600 million inhabitants, in whom a significant growth in population is combined with the progressive ageing of the population. This part of the world poses great challenges for general and respiratory health. Most of the countries have significant, or even greater, rates of chronic respiratory diseases or exposure to risk. Human resources in healthcare are not readily available, particularly in the area of respiratory disease specialists. Academic training centers are few and even non-existent in the majority of the countries. The detailed analysis of these conditions provides a basis for reflection on the main challenges and proposals for the management and training of better human resources in this specialist area. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  18. Molecular Identification and Epidemiological Features of Human Adenoviruses Associated with Acute Respiratory Infections in Hospitalized Children in Southern China, 2012-2013.

    Science.gov (United States)

    Chen, Yi; Liu, Fanghua; Wang, Changbing; Zhao, Mingqi; Deng, Li; Zhong, Jiayu; Zhang, Yingying; Ye, Jun; Jing, Shuping; Cheng, Zetao; Guan, Yongxin; Ma, Yi; Sun, Yuanyuan; Zhu, Bing; Zhang, Qiwei

    2016-01-01

    Acute respiratory infections (ARI) are the major worldwide health problem associated with high morbidity and mortality rates. Human adenovirus (HAdV) is one of the most common pathogens associated with viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics. Total 4,130 children with ARI requiring hospitalization from 2012 to 2013 were retrospectively studied. Throat swab specimens were collected from each patient. Fluorescence Quantitative PCR was performed to detect adenovirus as well as other common ARI-related pathogens. The seven HAdV hypervariable regions (HVRs) of the hexon gene from fifty-seven HAdVs-positive samples collected in the seasonal peaks were sequenced. Phylogenetic analysis of HVRs was also conducted to confirm the molecular types and genetic variation. In addition, epidemiological features and co-infection with other human respiratory pathogens were investigated and analyzed. Of 4,130 hospitalized pediatric patients tested, the positive rates of respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and HAdV were 13.7%, 13.2%, and 12.0%, respectively. The HAdV positive patients accounted for 7.9%, 17.2%, 17.5% and 10.7% in age groups infected with other respiratory pathogens (84/495, 17.0%). The most common co-infection pathogens with HAdV were MP (57.1%) and Human Bocavirus (HBoV) (16.7%). The majority of HAdV infected patients were totally recovered (96.9%, 480/495); However, four (0.8%) patients, who were previously healthy and at the age of 2 years or younger died of pneumonia. Seasonal peaks of HAdV infection occurred in the summer season of 2012 and 2013; the predominant HAdV type was HAdV-3 (70%), followed by HAdV-7 (28%). These epidemiological features were different from those in Northern China. The HAdV-55 was identified and reported for the first time in Guangzhou metropolitan area. Phylogenetic analysis indicated that all the HVR sequences of the hexon gene

  19. Molecular Identification and Epidemiological Features of Human Adenoviruses Associated with Acute Respiratory Infections in Hospitalized Children in Southern China, 2012-2013.

    Directory of Open Access Journals (Sweden)

    Yi Chen

    Full Text Available Acute respiratory infections (ARI are the major worldwide health problem associated with high morbidity and mortality rates. Human adenovirus (HAdV is one of the most common pathogens associated with viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics.Total 4,130 children with ARI requiring hospitalization from 2012 to 2013 were retrospectively studied. Throat swab specimens were collected from each patient. Fluorescence Quantitative PCR was performed to detect adenovirus as well as other common ARI-related pathogens. The seven HAdV hypervariable regions (HVRs of the hexon gene from fifty-seven HAdVs-positive samples collected in the seasonal peaks were sequenced. Phylogenetic analysis of HVRs was also conducted to confirm the molecular types and genetic variation. In addition, epidemiological features and co-infection with other human respiratory pathogens were investigated and analyzed.Of 4,130 hospitalized pediatric patients tested, the positive rates of respiratory syncytial virus (RSV, Mycoplasma pneumoniae (MP, and HAdV were 13.7%, 13.2%, and 12.0%, respectively. The HAdV positive patients accounted for 7.9%, 17.2%, 17.5% and 10.7% in age groups <1, 1-3, 3-6 and 6-14 years, respectively. Eighty-four HAdV positive children were co-infected with other respiratory pathogens (84/495, 17.0%. The most common co-infection pathogens with HAdV were MP (57.1% and Human Bocavirus (HBoV (16.7%. The majority of HAdV infected patients were totally recovered (96.9%, 480/495; However, four (0.8% patients, who were previously healthy and at the age of 2 years or younger died of pneumonia. Seasonal peaks of HAdV infection occurred in the summer season of 2012 and 2013; the predominant HAdV type was HAdV-3 (70%, followed by HAdV-7 (28%. These epidemiological features were different from those in Northern China. The HAdV-55 was identified and reported for the first time in Guangzhou

  20. CFD heat transfer simulation of the human upper respiratory tract for oronasal breathing condition

    Directory of Open Access Journals (Sweden)

    Kambiz Farahmand

    2012-01-01

    Full Text Available Injuries due to inhalation of hot gas are commonly encountered when dealing with fire and combustible material, which is harmful and threatens human life. In the literature, various studies have been conducted to investigate heat and mass transfer characteristics in the human respiratory tract (HRT. This study focuses on assessing the injury taking place in the upper human respiratory tract and identifying acute tissue damage, based on level of exposure. A three-dimensional heat transfer simulation is performed using Computational Fluid Dynamics (CFD software to study the temperature profile through the upper HRT consisting of the nasal cavity, oral cavity, trachea, and the first two generations of bronchi. The model developed is for the simultaneous oronasal breathing during the inspiration phase with a high volumetric flow rate of 90 liters/minute and the inspired air temperature of 100 degrees Celsius. The geometric model depicting the upper HRT is generated based on the data available and literature cited. The results of the simulation give the temperature distribution along the center and the surface tissue of the respiratory tract. This temperature distribution will help to assess the level of damage induced in the upper respiratory tract and appropriate treatment for the damage. A comparison of nasal breathing, oral breathing, and oronasal breathing is performed. Temperature distribution can be utilized in the design of the respirator systems where inlet temperature is regulated favoring the human body conditions.

  1. Research Summary 3-D Computational Fluid Dynamics (CFD) Model Of The Human Respiratory System

    Science.gov (United States)

    The U.S. EPA’s Office of Research and Development (ORD) has developed a 3-D computational fluid dynamics (CFD) model of the human respiratory system that allows for the simulation of particulate based contaminant deposition and clearance, while being adaptable for age, ethnicity,...

  2. TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS

    Science.gov (United States)

    TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS. Zhe Zhang*, Huawei Shi, Clement Kleinstreuer, Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910; Chong S. Kim, National Health and En...

  3. ROLE OF MONOCYTES AND EOSINOPHILS IN RESPIRATORY SYNCTIAL VIRUS (RSV) INFECTION

    Science.gov (United States)

    Role of Monocytes and Eosinophils in Respiratory Syncytial Virus (RSV) InfectionJoleen M. Soukup and Susanne Becker US Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711;...

  4. Parainfluenza virus as a cause of acute respiratory infection in hospitalized children.

    Science.gov (United States)

    Pecchini, Rogério; Berezin, Eitan Naaman; Souza, Maria Cândida; Vaz-de-Lima, Lourdes de Andrade; Sato, Neuza; Salgado, Maristela; Ueda, Mirthes; Passos, Saulo Duarte; Rangel, Raphael; Catebelota, Ana

    2015-01-01

    Human parainfluenza viruses account for a significant proportion of lower respiratory tract infections in children. To assess the prevalence of Human parainfluenza viruses as a cause of acute respiratory infection and to compare clinical data for this infection against those of the human respiratory syncytial virus. A prospective study in children younger than five years with acute respiratory infection was conducted. Detection of respiratory viruses in nasopharyngeal aspirate samples was performed using the indirect immunofluorescence reaction. Length of hospital stay, age, clinical history and physical exam, clinical diagnoses, and evolution (admission to Intensive Care Unit or general ward, discharge or death) were assessed. Past personal (premature birth and cardiopathy) as well as family (smoking and atopy) medical factors were also assessed. A total of 585 patients were included with a median age of 7.9 months and median hospital stay of six days. No difference between the HRSV+ and HPIV+ groups was found in terms of age, gender or length of hospital stay. The HRSV+ group had more fever and cough. Need for admission to the Intensive Care Unit was similar for both groups but more deaths were recorded in the HPIV+ group. The occurrence of parainfluenza peaked during the autumn in the first two years of the study. Parainfluenza was responsible for significant morbidity, proving to be the second-most prevalent viral agent in this population after respiratory syncytial virus. No difference in clinical presentation was found between the two groups, but mortality was higher in the HPIV+ group. Copyright © 2015. Published by Elsevier Editora Ltda.

  5. Spirometry filters can be used to detect exhaled respiratory viruses.

    Science.gov (United States)

    Mitchell, Alicia B; Mourad, Bassel; Tovey, Euan; Buddle, Lachlan; Peters, Matthew; Morgan, Lucy; Oliver, Brian G

    2016-09-26

    Respiratory viruses are very common in the community and contribute to the burden of illness for patients with chronic respiratory diseases, including acute exacerbations. Traditional sampling methods are invasive and problematic to repeat. Accordingly, we explored whether respiratory viruses could be isolated from disposable spirometry filters and whether detection of viruses in this context represented presence in the upper or lower respiratory tract. Discovery (n  =  53) and validation (n  =  49) cohorts were recruited from a hospital outpatient department during two different time periods. Spirometry mouthpiece filters were collected from all participants. Respiratory secretions were sampled from the upper and lower respiratory tract by nasal washing (NW), sputum, and bronchoalveolar lavage (BAL). All samples were examined using RT-PCR to identify a panel of respiratory viruses (rhinovirus, respiratory syncytial virus, influenza A, influenza B, parainfluenza virus 1, 2 & 3, and human metapneumovirus). Rhinovirus was quantified using qPCR. Paired filter-NW samples (n  =  29), filter-sputum samples (n  =  24), filter-BAL samples (n  =  39) and filter-NW-BAL samples (n  =  10) provided a range of comparisons. At least one virus was detected in any sample in 85% of participants in the discovery cohort versus 45% in the validation cohort. Overall, 72% of viruses identified in the paired comparator method matched those detected in spirometry filters. There was a high correlation between viruses identified in spirometry filters compared with viruses identified in both the upper and lower respiratory tract using traditional sampling methods. Our results suggest that examination of spirometry filters may be a novel and inexpensive sampling method for the presence of respiratory viruses in exhaled breath.

  6. Human bocavirus isolated from children with acute respiratory tract infections in Korea, 2010-2011.

    Science.gov (United States)

    Ahn, Jong Gyun; Choi, Seong Yeol; Kim, Dong Soo; Kim, Ki Hwan

    2014-12-01

    Human bocavirus (HBoV) was first recognized in respiratory samples in 2005. The clinical importance of HBoV infection remains unclear. This report describes the clinical features and molecular phylogeny of HBoV isolates in children with acute respiratory infections. Nasopharyngeal aspirates were obtained from 1,528 children with acute respiratory infections between 2010 and 2011. Respiratory samples were screened for HBoV by multiplex PCR. A phylogenetic analysis of the HBoV VP1/VP2 gene was also undertaken. HBoV was detected in 187 (12.2%) of the 1,528 patients with a peak incidence of infection observed in patients aged 12-24 months. Coinfection with other respiratory viruses was observed in 107 (57.2%) of the HBoV-positive children. The peak of HBoV activity occurred during the month of June in both 2010 and 2011. A higher previous history of wheezing (P = 0.016), a higher frequency of chest retraction (P respiratory symptom score (P = 0.002), and a longer duration of hospital stay (P = 0.021) were observed in HBoV-positive children compared with the HBoV-negative group. Phylogenetic analysis showed all 187 HBoV-positive isolates were identified as HBoV 1, indicating minimal sequence variations among the isolates. A single lineage of HBoV 1 was found to have circulated in children with acute respiratory infections between 2010 and 2011 and was associated with several clinical characteristics including age, seasonality, and clinical severity with retraction, wheezing, and longer hospitalization. The clinical relevance of the minimal sequence variations of HBoV remains to be determined. © 2014 Wiley Periodicals, Inc.

  7. Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset.

    Science.gov (United States)

    Chen, Zhe; Bao, Linlin; Chen, Cong; Zou, Tingting; Xue, Ying; Li, Fengdi; Lv, Qi; Gu, Songzhi; Gao, Xiaopan; Cui, Sheng; Wang, Jianmin; Qin, Chuan; Jin, Qi

    2017-06-15

    Middle East respiratory syndrome coronavirus (MERS-CoV) infection in humans is highly lethal, with a fatality rate of 35%. New prophylactic and therapeutic strategies to combat human infections are urgently needed. We isolated a fully human neutralizing antibody, MCA1, from a human survivor. The antibody recognizes the receptor-binding domain of MERS-CoV S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4). To our knowledge, this study is the first to report a human neutralizing monoclonal antibody that completely inhibits MERS-CoV replication in common marmosets. Monotherapy with MCA1 represents a potential alternative treatment for human infections with MERS-CoV worthy of evaluation in clinical settings. © Crown copyright 2017.

  8. Human milk reduces outpatient upper respiratory symptoms in premature infants during their first year of life.

    Science.gov (United States)

    Blaymore Bier, Jo-Ann; Oliver, Tanya; Ferguson, Anne; Vohr, Betty R

    2002-01-01

    To determine if ingestion of human milk after discharge reduces symptoms of infections in premature infants. Follow-up of 39 infants with birth weights milk and 15 of whom received only formula after discharge, was carried out. Mothers were given a calendar on which they recorded any signs of infections and feeding and day-care information. Data were collected at 1 month after discharge and at 3, 7, and 12 months corrected age. Results show no differences between groups in birth weight, gestation, gender, maternal age, parental tobacco use, number of siblings, and day-care attendance. Socioeconomic status score was higher in the human milk group. Infants who received human milk had fewer days of upper respiratory symptoms at 1 month after discharge (pmilk post discharge is associated with a reduction of upper respiratory symptoms in premature infants during their first year of life.

  9. The significance of Candida in the human respiratory tract: our evolving understanding.

    Science.gov (United States)

    Pendleton, Kathryn M; Huffnagle, Gary B; Dickson, Robert P

    2017-04-01

    Candida is an opportunistic pathogen and the most commonly isolated fungal genus in humans. Though Candida is often detected in respiratory specimens from humans with and without lung disease, its significance remains undetermined. While historically considered a commensal organism with low virulence potential, the status of Candida as an innocent bystander has recently been called into question by both clinical observations and animal experimentation. We here review what is currently known and yet to be determined about the clinical, microbiological and pathophysiological significance of the detection of Candida spp. in the human respiratory tract. Published by Oxford University Press on behalf of FEMS 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. Viral etiology of respiratory infections in children under 5 years old living in tropical rural areas of Senegal: The EVIRA project.

    Science.gov (United States)

    Niang, Mbayame Ndiaye; Diop, Ousmane M; Sarr, Fatoumata Diene; Goudiaby, Deborah; Malou-Sompy, Hubert; Ndiaye, Kader; Vabret, Astrid; Baril, Laurence

    2010-05-01

    Acute respiratory infection is one of the leading causes of child morbidity, especially in developing countries. Viruses are recognized as the predominant causative agents of acute respiratory infections. In Senegal, few data concerning the causes of respiratory infections are available, and those known relate mainly to classical influenza infections. Clinical and virological surveillance of acute respiratory infections was carried out in a rural community in children less than 5 years old. A standardized questionnaire was used and a nasopharyngeal swab sample was collected from each patient. These samples were tested for the detection of 20 respiratory viruses by multiplex RT-PCR or by viral culture. A total of 82 acute respiratory episodes were included, and 48 (58.5%) were found to be positive, with a total of 55 viral detections; several samples were positive for two (n = 5) or 3 (n = 1) viruses. Ten different viruses were identified: influenza viruses A, B, and C (n = 25), human respiratory syncytial virus type A (n = 13), rhinoviruses (n = 8), human coronaviruses type 229E and NL63 (n = 6), parainfluenza viruses 3 and 4 (n = 2), and bocavirus (n = 1). These results provide evidence on the importance and the diversity of viruses as causative agents of acute respiratory infections in children living in a rural community in Senegal. The establishment of sentinel surveillance sites could help estimate the burden of acute respiratory infection in the pediatric population and should help prepare the health care systems to identify and respond to new viral respiratory emergencies.

  11. Respiratory sinus arrhythmia stabilizes mean arterial blood pressure at high-frequency interval in healthy humans.

    Science.gov (United States)

    Elstad, Maja; Walløe, Lars; Holme, Nathalie L A; Maes, Elke; Thoresen, Marianne

    2015-03-01

    Arterial blood pressure variations are an independent risk factor for end organ failure. Respiratory sinus arrhythmia (RSA) is a sign of a healthy cardiovascular system. However, whether RSA counteracts arterial blood pressure variations during the respiratory cycle remains controversial. We restricted normal RSA with non-invasive intermittent positive pressure ventilation (IPPV) to test the hypothesis that RSA normally functions to stabilize mean arterial blood pressure. Ten young volunteers were investigated during metronome-paced breathing and IPPV. Heart rate (ECG), mean arterial blood pressure and left stroke volume (finger arterial pressure curve) and right stroke volume (pulsed ultrasound Doppler) were recorded, while systemic and pulmonary blood flow were calculated beat-by-beat. Respiratory variations (high-frequency power, 0.15-0.40 Hz) in cardiovascular variables were estimated by spectral analysis. Phase angles and correlation were calculated by cross-spectral analysis. The magnitude of RSA was reduced from 4.9 bpm(2) (95% CI 3.0, 6.2) during metronome breathing to 2.8 bpm(2) (95% CI 1.1, 5.0) during IPPV (p = 0.03). Variations in mean arterial blood pressure were greater (2.3 mmHg(2) (95% CI 1.4, 3.9) during IPPV than during metronome breathing (1.0 mmHg(2) [95% CI 0.7, 1.3]) (p = 0.014). Respiratory variations in right and left stroke volumes were inversely related in the respiratory cycle during both metronome breathing and IPPV. RSA magnitude is lower and mean arterial blood pressure variability is greater during IPPV than during metronome breathing. We conclude that in healthy humans, RSA stabilizes mean arterial blood pressure at respiratory frequency.

  12. Differential expression of the MERS-coronavirus receptor in the upper respiratory tract of humans and dromedary camels

    NARCIS (Netherlands)

    Widagdo, W; Raj, V Stalin; Schipper, Debby; Kolijn, Kimberley; van Leenders, Geert J L H; Bosch, Berend J; Bensaid, Albert; Segalés, Joaquim; Baumgärtner, Wolfgang; Osterhaus, Albert D M E; Koopmans, Marion P; van den Brand, Judith M A; Haagmans, Bart L

    Middle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV receptor - dipeptidyl peptidase 4 (DPP4) - is expressed in the upper respiratory tract epithelium of camels but not

  13. Central respiratory chemosensitivity and cerebrovascular CO2 reactivity: a rebreathing demonstration illustrating integrative human physiology.

    Science.gov (United States)

    MacKay, Christina M; Skow, Rachel J; Tymko, Michael M; Boulet, Lindsey M; Davenport, Margie H; Steinback, Craig D; Ainslie, Philip N; Lemieux, Chantelle C M; Day, Trevor A

    2016-03-01

    One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations have the added benefit of being able to show multiple organ system integration. Many research techniques can also serve as effective demonstrations of integrative human physiology. The "Duffin" hyperoxic rebreathing test is often used in research settings as a test of central respiratory chemosensitivity and cerebrovascular reactivity to CO2. We aimed to demonstrate the utility of the hyperoxic rebreathing test for both respiratory and cerebrovascular responses to increases in CO2 and illustrate the integration of the respiratory and cerebrovascular systems. In the present article, methods such as spirometry, respiratory gas analysis, and transcranial Doppler ultrasound are described, and raw data traces can be adopted for discussion in a tutorial setting. If educators have these instruments available, instructions on how to carry out the test are provided so students can collect their own data. In either case, data analysis and quantification are discussed, including principles of linear regression, calculation of slope, the coefficient of determination (R(2)), and differences between plotting absolute versus normalized data. Using the hyperoxic rebreathing test as a demonstration of the complex interaction and integration between the respiratory and cerebrovascular systems provides senior undergraduate, graduate, and medical students with an advanced understanding of the integrative nature of human physiology. Copyright © 2016 The American Physiological Society.

  14. Numerical Simulation of Hemodynamic and Physiological Responses of Human Cardiovascular and Respiratory System under Drugs Administration

    Czech Academy of Sciences Publication Activity Database

    Převorovská, Světlana; Maršík, František

    2004-01-01

    Roč. 4, č. 4 (2004), s. 295-304 ISSN 1567-8822 R&D Projects: GA ČR(CZ) GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z2076919 Keywords : human cardiovascular and respiratory system * baroreflex and chemoreflex control * physiologically based pharmacokinetic model Subject RIV: BK - Fluid Dynamics

  15. Particle deposition and clearance of atmospheric particles in the human respiratory tract during LACE 98

    Science.gov (United States)

    Bundke, U.; Hänel, G.

    2003-04-01

    During the LACE 98footnote{Lindenberg Aerosol Characterization Experiment, (Germany) 1998} experiment microphysical, chemical and optical properties of atmospheric particles were measured by several groups. (Bundke et al.). The particle deposition and clearance of the particles in the human respiratory tract was calculated using the ICRP (International Commission on Radiological Protection) deposition and clearance model (ICRP 1994). Particle growth as function of relative humidity outside the body was calculated from measurement data using the model introduced by Bundke et al.. Particle growth inside the body was added using a non-equilibrium particle growth model. As a result of the calculations, time series of the total dry particle mass and -size distribution were obtained for all compartments of the human respiratory tract defined by ICRP 1994. The combined ICRP deposition and clearance model was initialized for different probationers like man, woman, children of different ages and several circumstances like light work, sitting, sleeping etc. Keeping the conditions observed during LACE 98 constant a approximation of the aerosol burdens of the different compartments was calculated up to 4 years of exposure and compared to the results from Snipes et al. for the "Phoenix" and "Philadelphia" aerosol. References: footnotesize{ Bundke, U. et al.,it{Aerosol Optical Properties during the Lindenberg Aerosol Characterization Experiment (LACE 98)} ,10.1029/2000JD000188, JGR, 2002 ICRP,it{Human Respiratory Tract Model for Radiological Protection, Bd. ICRP Publication 66}, Annals of the ICRP, 24,1-3, Elsevier Science, Ocford, 1994 Snipes et al. ,it{The 1994 ICRP66 Human Respiratory Tract Model as a Tool for predicting Lung Burdens from Exposure to Environmental Aerosols}, Appl. Occup. Environ. Hyg., 12, 547-553,1997}

  16. Risk Factors for Hospitalization for Respiratory Syncytial Virus Infection

    DEFF Research Database (Denmark)

    Haerskjold, Ann; Kristensen, Kim; Kamper-Jørgensen, Mads

    2016-01-01

    of gestational age. Plurality was associated with a decreased risk in children born between 23 and 36 weeks of gestation, whereas young maternal age, maternal asthma, single parenthood, maternal smoking, being born small for gestational age, Caesarian section, male gender and day care were associated...... with an increased risk of hospitalization for RSV infection in term children. In postterm children, young maternal age, male sex, being born small for gestational age and maternal smoking were associated with an increased risk of hospitalization for RSV. Asthma hospitalization before the RSV infection and siblings...

  17. Caesarean Section and Hospitalization for Respiratory Syncytial Virus Infection

    DEFF Research Database (Denmark)

    Kristensen, Kim; Fisker, Niels; Haerskjold, Ann

    2015-01-01

    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...

  18. the epidemiology of respiratory syncytial virus (rsv) infections in ...

    African Journals Online (AJOL)

    countries and correlates closely with infant mortality rates.' ARI is an ... irnmunoglobuhn therapy there has been increased interest in the development of ..... vitamin A: a randomised, placebo-controlIed trial in Santiago, Chile. Pediatr Infect Dis ...

  19. Development of respiratory syncytial virus (RSV) vaccines for infants.

    Science.gov (United States)

    Gerretsen, Hannah E; Sande, Charles J

    2017-06-01

    2017 will mark the 60 th anniversary since the first isolation of RSV in children. In spite of concerted efforts over all these years, the goal of developing an effective vaccine against paediatric RSV disease has remained elusive. One of the main hurdles standing in the way of an effective vaccine is the fact that the age incidence of severe disease peaks within the first 3 months of life, providing limited opportunity for intervention. In addition to this complexity, the spectre of failed historical vaccines, which increased the risk of illness and death upon subsequent natural infection, has substantially increased the safety criteria against which modern vaccines will be assessed. This review traces the history of RSV vaccine development for young infants and analyses the potential reasons for the failure of historic vaccines. It also discusses recent breakthroughs in vaccine antigen design and the progressive evolution of platforms for the delivery of these antigens to seronegative infants. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  20. [Detection and clinical analysis of acute lower respiratory tract infection with human coronaviruses in children in Beijing area 2007-2015].

    Science.gov (United States)

    Qian, Yi; Xie, Zhengde; Ren, Lili; Liu, Chunyan; Xiao, Yan; Xu, Baoping; Yang, Yan; Qian, Suyun; Geng, Rong; Shen, Kunling

    2015-09-01

    To investigate human coronaviruses (HCoVs) infection in children with acute lower respiratory tract infection(ALRTI)and to explore the clinical features of ALRTI caused by HCoVs in children. Totally 4 371 children with clinical diagnosis of ALRTI during the period from March 2007 to February 2015 seen in Beijing Children's Hospital were recruited into this study. Patients were divided into 4 groups by age, including 1 890 cases in respiratory viruses including HCoVs (including HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1), respiratory syncytial virus (RSV) and so on. Clinical features of ALRTI with single HCoVs infection were analyzed and compared with hospitalized ALRTI cases with single RSV infection in the same period. (1) Totally 2 895 cases were positive for at least one virus in this study in 4 371 ALRTI patients (positive rate 66.23%), in which 147 cases were positive for HCoVs infection (positive rate 3.36%). (2) Positive rates of HCoVs in each year from 2007 to 2014 were 6.11%, 3.79%, 4.69%, 4.31%, 2.38% 2.10%, 0.77% and 2.65%, respectively. The mean positive rates of HCoVs for each month from January to December were 2.53%, 2.12%, 3.63%, 6.68%, 1.53%, 3.77%, 3.92%, 3.00%, 2.15%, 5.26%, 3.01% and 2.80%. (3) Detection results of each subtypes of HCoVs in total 4 371 pediatric ALRTI patients were: 48 cases positive for HCoV-OC43(1.10%), 32 cases positive for HCoV-229E(0.73%), 25 cases positive for HCoV-NL63 (0.57%), 27 cases positive for HCoV-HKU1 (0.62%). (4) Positive rates of HCoVs infection in infection of HCoVs in this study, of which 12 cases were diagnosed as bronchopneumonia, 3 cases developed acute laryngeal obstruction, 2 cases had acute bronchial asthma attack. Common clinical manifestations included cough (14 cases), gasping (13 cases), dyspnea (9 cases), fever (6 cases), hoarseness (4 cases), laryngeal stridor (4 cases) and abnormality on chest X-ray (including fuzzy lung texture, patchy shadow and consolidation) (12 cases). (6) There were no

  1. Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

    Science.gov (United States)

    Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

    2010-01-01

    Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

  2. Human respiratory tract model for radiological protection: A revision of the ICRP Dosimetric Model for the Respiratory System

    International Nuclear Information System (INIS)

    Bair, W.J.

    1989-01-01

    In 1984, the International Commission on Radiological Protection (ICRP) appointed a task group of Committee 2 to review and revise, as necessary, the ICRP Dosimetric Model for the Respiratory System. The model was originally published in 1966, modified slightly in Publication No. 19, and again in Publication No. 30 (in 1979). The task group concluded that research during the past 20 y suggested certain deficiencies in the ICRP Dosimetric Model for the Respiratory System. Research has also provided sufficient information for a revision of the model. The task group's approach has been to review, in depth, morphology and physiology of the respiratory tract; deposition of inhaled particles in the respiratory tract; clearance of deposited materials; and the nature and specific sites of damage to the respiratory tract caused by inhaled radioactive substances. This review has led to a redefinition of the regions of the respiratory tract for dosimetric purposes. The redefinition has a morphologic and physiological basis and is consistent with observed deposition and clearance of particles and with resultant pathology. Regions, as revised, are the extrathoracic (E-T) region, comprising the nasal and oral regions, the pharynx, larynx, and upper part of the trachea; the fast-clearing thoracic region (T[f]), comprising the remainder of the trachea and bronchi; and the slow-clearing thoracic region (T[s]), comprising the bronchioles, alveoli, and thoracic lymph nodes. A task group report will include models for calculating radiation doses to these regions of the respiratory tract following inhalation of representative alpha-, beta-, and gamma-emitting particulate and gaseous radionuclides. The models may be implemented as a package of computer codes available to a wide range of users

  3. Human milk 90K (Mac-2 BP): possible protective effects against acute respiratory infections.

    Science.gov (United States)

    Fornarini, B; Iacobelli, S; Tinari, N; Natoli, C; De Martino, M; Sabatino, G

    1999-01-01

    Eighty-six children fed human milk were followed prospectively from birth to 12 months of age to assess the effect of milk 90K, a secreted glycoprotein with immune-stimulatory properties, on development of acute respiratory infections (ARI). The level of human milk 90K was inversely related to episodes of ARI (r = - 0.34; P = 0.001). The average 90K level in human milk fed to children who did not develop ARI was significantly higher than in milk fed to children in whom infection occurred on multiple occasions (156.6 +/- 144.8 microg/ml versus 70.9 +/- 92.3 microg/ml; P = 0.001). These data suggest that the protective effects of human milk against ARI may be due in part to immune maturation effects by secreted 90K.

  4. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

    Science.gov (United States)

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

    2014-12-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

  5. The role of infections and coinfections with newly identified and emerging respiratory viruses in children

    Directory of Open Access Journals (Sweden)

    Debiaggi Maurizia

    2012-10-01

    Full Text Available Abstract Acute respiratory infections are a major cause of morbidity in children both in developed and developing countries. A wide range of respiratory viruses, including respiratory syncytial virus (RSV, influenza A and B viruses, parainfluenza viruses (PIVs, adenovirus, rhinovirus (HRV, have repeatedly been detected in acute lower respiratory tract infections (LRTI in children in the past decades. However, in the last ten years thanks to progress in molecular technologies, newly discovered viruses have been identified including human Metapneumovirus (hMPV, coronaviruses NL63 (HcoV-NL63 and HKU1 (HcoV-HKU1, human Bocavirus (HBoV, new enterovirus (HEV, parechovirus (HpeV and rhinovirus (HRV strains, polyomaviruses WU (WUPyV and KI (KIPyV and the pandemic H1N1v influenza A virus. These discoveries have heavily modified previous knowledge on respiratory infections mainly highlighting that pediatric population is exposed to a variety of viruses with similar seasonal patterns. In this context establishing a causal link between a newly identified virus and the disease as well as an association between mixed infections and an increase in disease severity can be challenging. This review will present an overview of newly recognized as well as the main emerging respiratory viruses and seek to focus on the their contribution to infection and co-infection in LRTIs in childhood.

  6. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection.

    Directory of Open Access Journals (Sweden)

    Trevenan Walther

    2013-03-01

    Full Text Available The first step in influenza infection of the human respiratory tract is binding of the virus to sialic (Sia acid terminated receptors. The binding of different strains of virus for the receptor is determined by the α linkage of the sialic acid to galactose and the adjacent glycan structure. In this study the N- and O-glycan composition of the human lung, bronchus and nasopharynx was characterized by mass spectrometry. Analysis showed that there was a wide spectrum of both Sia α2-3 and α2-6 glycans in the lung and bronchus. This glycan structural data was then utilized in combination with binding data from 4 of the published glycan arrays to assess whether these current glycan arrays were able to predict replication of human, avian and swine viruses in human ex vivo respiratory tract tissues. The most comprehensive array from the Consortium for Functional Glycomics contained the greatest diversity of sialylated glycans, but was not predictive of productive replication in the bronchus and lung. Our findings indicate that more comprehensive but focused arrays need to be developed to investigate influenza virus binding in an assessment of newly emerging influenza viruses.

  7. [Study of etiologic factors of infectious diseases of respiratory tract in school-age children during period of remission of a respiratory disease].

    Science.gov (United States)

    Maĭorov, R V; Chereshneva, M V; Chereshnev, V A

    2013-01-01

    Detect features of microflora of upper respiratory tract on the example of flora of palatine tonsils and level of antibodies against intracellular parasites as markers of etiologic factors of respiratory infections in school-age children in remission period. 466 children from frequently and episodically ill groups were examined. Bacteriologic study of smears from the surface of palatine tonsils was carried out in all the children. By using EIA with the corresponding commercial test systems IgG level against Herpes simplex virus, Cytomegalovirus, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Human respiratory syncytial virus was determined in blood sera according to instruction manual. During remission period of infectious process in the structure of microflora of upper respiratory tract in frequently ill children characteristic differences from their episodically ill peers were detected. In children with frequent respiratory infections a higher occurrence of antibodies against intracellular causative agents of these diseases was also detected. In the group of frequently ill, a direct correlation between frequency of infectious diseases of respiratory tract and occurrence of carriage of pathogenic and opportunistic microorgan isms as well as increase of antibodies against Herpesviridae, Cytomegalovirus, C. pneumoniae and M. pneumoniae was detected. Higher occurrence ofintra- and extra-cellular infectious agents as well as their associations may be considered as one of the reasons of insufficient effectiveness of prophylaxis measures in frequently ill children.

  8. Effects of Long-Term Dust Exposure on Human Respiratory System Health in Minqin County, China.

    Science.gov (United States)

    Wang, Jinyu; Li, Sheng; Wang, Shigong; Shang, Kezheng

    2015-01-01

    The aim of this study was to assess the effects of long-term sand dust exposure on human respiratory health. Dust events break out frequently in Minqin County, northwest China, whereas Pingliang City, northwest China, is rarely influenced by dust events. Therefore, Minqin and Pingliang were selected as sand dust exposure region and control area, respectively. The incidence of respiratory system diseases and symptoms was determined through a structured respiratory health questionnaire (ATS-DLD-78-A) and personal interviews. The subjects comprised 728 farmers (Minqin, 424; Pingliang, 304) aged 40 years or older, who had nondocumented occupational history to industrial dust exposure. Prevalences (odds ratio [OR], 95% confidence interval [CI]) of chronic rhinitis, chronic bronchitis, and chronic cough increased 9.6% (3.141, 1.776-5.555), 7.5% (2.468, 1.421-4.286), and 10.2% (1.787, 1.246-2.563) in Minqin comparison with Pingliang, respectively, and the differences were significant (p <.01).

  9. Genetic diversity of human metapneumovirus in hospitalized children with acute respiratory infections in Croatia.

    Science.gov (United States)

    Jagušić, Maja; Slović, Anamarija; Ljubin-Sternak, Sunčanica; Mlinarić-Galinović, Gordana; Forčić, Dubravko

    2017-11-01

    Human metapneumovirus (HMPV) is recognized as a global and frequent cause of acute respiratory tract infections among people of all ages. The objectives of this study were molecular epidemiology and evolutionary analysis of HMPV strains which produced moderate and severe acute respiratory tract infections in children in Croatia during four consecutive seasons (2011-2014). A total of 117 HMPV-positive samples collected from hospitalized pediatric patients presenting with acute respiratory tract infections and tested by direct immunofluorescence assay were first analyzed by amplifying a part of the F gene. Sixteen samples were further analyzed based on complete F, G, and SH gene sequences. HMPV genome was identified in 92 of 117 samples (78%) and the circulation of multiple lineages of HMPV was confirmed. In 2011, 2012, and 2014, subgroups A2 and B2 co-circulated, while B1 gained prevalence in 2013 and 2014. The study established the presence of a novel subcluster A2c in Croatia. This subcluster has only recently been detected in East and Southeast Asia. This study provides new insights into epidemiology and genetic diversity of HMPV in this part of Europe. © 2017 Wiley Periodicals, Inc.

  10. Phylogenic analysis of human bocavirus detected in children with acute respiratory infection in Yaounde, Cameroon.

    Science.gov (United States)

    Kenmoe, Sebastien; Vernet, Marie-Astrid; Njankouo-Ripa, Mohamadou; Penlap, Véronique Beng; Vabret, Astrid; Njouom, Richard

    2017-07-17

    Human Bocavirus (HBoV) was first identified in 2005 and has been shown to be a common cause of respiratory infections and gastroenteritis in children. In a recent study, we found that 10.7% of children with acute respiratory infections (ARI) were infected by HBoV. Genetic characterization of this virus remains unknown in Central Africa, particularly in Cameroon Leeding us to evaluate the molecular characteristics of HBoV strains in Cameroonian children with ARI. Phylogenetic analysis of partial HBoV VP1/2 sequences showed a low level of nucleotide variation and the circulation of HBoV genotype 1 (HBoV-1) only. Three clades were obtained, two clustering with each of the reference strains ST1 and ST2, and a third group consisting of only Cameroon strains. By comparing with the Swedish reference sequences, ST1 and ST2, Cameroon sequences showed nucleotide and amino acid similarities of respectively 97.36-100% and 98.35-100%. These results could help improve strategies for monitoring and control of respiratory infections in Cameroon.

  11. A diverse group of previously unrecognized human rhinoviruses are common causes of respiratory illnesses in infants.

    Directory of Open Access Journals (Sweden)

    Wai-Ming Lee

    2007-10-01

    Full Text Available Human rhinoviruses (HRVs are the most prevalent human pathogens, and consist of 101 serotypes that are classified into groups A and B according to sequence variations. HRV infections cause a wide spectrum of clinical outcomes ranging from asymptomatic infection to severe lower respiratory symptoms. Defining the role of specific strains in various HRV illnesses has been difficult because traditional serology, which requires viral culture and neutralization tests using 101 serotype-specific antisera, is insensitive and laborious.To directly type HRVs in nasal secretions of infants with frequent respiratory illnesses, we developed a sensitive molecular typing assay based on phylogenetic comparisons of a 260-bp variable sequence in the 5' noncoding region with homologous sequences of the 101 known serotypes. Nasal samples from 26 infants were first tested with a multiplex PCR assay for respiratory viruses, and HRV was the most common virus found (108 of 181 samples. Typing was completed for 101 samples and 103 HRVs were identified. Surprisingly, 54 (52.4% HRVs did not match any of the known serotypes and had 12-35% nucleotide divergence from the nearest reference HRVs. Of these novel viruses, 9 strains (17 HRVs segregated from HRVA, HRVB and human enterovirus into a distinct genetic group ("C". None of these new strains could be cultured in traditional cell lines.By molecular analysis, over 50% of HRV detected in sick infants were previously unrecognized strains, including 9 strains that may represent a new HRV group. These findings indicate that the number of HRV strains is considerably larger than the 101 serotypes identified with traditional diagnostic techniques, and provide evidence of a new HRV group.

  12. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral

    Directory of Open Access Journals (Sweden)

    Claire M. Smith

    2016-08-01

    Full Text Available Defective interfering (DI viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8 was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1; it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral.

  13. Respiratory infections in elderly people: Viral role in a resident population of elderly care centers in Lisbon, winter 2013–2014

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    Maria-Jesus Chasqueira

    2018-04-01

    Full Text Available Objective: The aim of this study was to analyze the etiology and clinical consequences of viral respiratory infections in 18 elderly care centers (ECC in Lisbon, which housed a total of 1022 residents. Methods: Nasopharyngeal swabs were collected whenever an elderly had symptoms of acute respiratory infections (ARI. PCR and RT-PCR were performed for influenza A/B, human parainfluenza virus 1–4, adenovirus, human metapneumovirus (HMPV, respiratory syncytial virus (RSV, rhinovirus, enterovirus, human coronavirus and human Bocavirus (HBoV. Array cards for atypical bacteria were also used in severe cases. Results: In total, 188 episodes of ARI were reported, being rhinovirus the most frequently detected (n = 53, followed by influenza A(H3 (n = 19 and HBoV (n = 14. Severe infections were reported in 19 patients, 11 of which were fatal, Legionela pneumophila, rhinovirus, HMPV and RSV associated with these fatalities. Nine influenza strains were analyzed, all antigenically dissimilar from vaccine strain 2013/14. “Age”, “HMPV” and “Respiratory disease” showed an association with severe infection. Conclusions: In this study an etiologic agent could be found in 60% of the acute respiratory episodes. These data provides information about the circulating viruses in ECC and highlights the importance of searching both viruses and atypical bacteria in severe ARI. Keywords: Elderly, Respiratory infections, Respiratory viruses, Legionella pneumophila, Elderly care centers, Real time PCR

  14. Etiology and Clinical Characteristics of Single and Multiple Respiratory Virus Infections Diagnosed in Croatian Children in Two Respiratory Seasons

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    Sunčanica Ljubin-Sternak

    2016-01-01

    Full Text Available The aim of this study was to determine the causative agent of acute respiratory infection (ARI in hospitalized children, as well as investigate the characteristics of ARIs with single and multiple virus detection in two respiratory seasons. In 2010 and 2015, nasopharyngeal and pharyngeal swabs from a total of 134 children, admitted to the hospital due to ARI, were tested using multiplex PCR. Viral etiology was established in 81.3% of the patients. Coinfection with two viruses was diagnosed in 27.6% of the patients, and concurrent detection of three or more viruses was diagnosed in 12.8% of the patients. The most commonly diagnosed virus in both seasons combined was respiratory syncytial virus (RSV (28.6%, followed by parainfluenza viruses (PIVs types 1–3 (18.4%, rhinovirus (HRV (14.3%, human metapneumovirus (10.1%, adenovirus (AdV (7.1%, influenza viruses types A and B (4.8%, and coronaviruses (4.2%. In 2015, additional pathogens were investigated with the following detection rate: enterovirus (13.2%, bocavirus (HBoV (10.5%, PIV-4 (2.6%, and parechovirus (1.3%. There were no statistical differences between single and multiple virus infection regarding patients age, localization of infection, and severity of disease (P>0.05. AdV, HRV, HBoV, and PIVs were significantly more often detected in multiple virus infections compared to the other respiratory viruses (P<0.001.

  15. Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

    2016-09-01

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

  16. Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

    2016-09-30

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

  17. Cytotoxicity of carbon nanohorns in different human cells of the respiratory system.

    Science.gov (United States)

    Schramm, Franziska; Lange, Martina; Hoppmann, Pia; Heutelbeck, Astrid

    2016-01-01

    One of the new synthetic carbon-based nanomaterials is carbon nanohorns (CNH). A potential risk for employees of production processes is an unintentional intake of these nanomaterials via inhalation. Once taken up, nanoparticles might interact with cells of different tissues as well as with intercellular substances. These interactions may have far-reaching consequences for human health. Currently, many gaps in available information on the CNH toxicological profile remain. The aim of this study was to determine the cytotoxicity of CNH particles on human epithelial cells of the respiratory system with special consideration given to different particle sizes. In all cell lines, cell viability was reduced after 24 h of exposure up to 60% and metabolic activity as evidenced by mitochondrial activity was lowered to 9% at a concentration of 1 g/L. The three respiratory cell lines differed in their sensitivity. The most robust cells were the bronchial epithelial cells. Further, particle size fractions induced different adverse effect strength, whereby no correlation between particle size fraction and toxicity was found. These findings demonstrate the need for further information regarding the behavior and effect strength of nanomaterial. To avoid the production of new harmful materials, a more comprehensive integration of results from toxicity studies in the development processes of engineered nanomaterials is recommended not only from an occupational viewpoint but also from an environmental perspective.

  18. A 3-year prospective study of the epidemiology of acute respiratory viral infections in hospitalized children in Shenzhen, China.

    Science.gov (United States)

    He, Ying; Lin, Guang-Yu; Wang, Qiong; Cai, Xiao-Ying; Zhang, Yin-Hui; Lin, Chuang-Xing; Lu, Chang-Dong; Lu, Xue-Dong

    2014-07-01

    The epidemiology of local viral etiologies is essential for the management of viral respiratory tract infections. Limited data are available in China to describe the epidemiology of viral respiratory infections, especially in small-medium cities and rural areas. To determine the viral etiology and seasonality of acute respiratory infections in hospitalized children, a 3-year study was conducted in Shenzhen, China. Nasopharyngeal aspirates from eligible children were collected. Influenza and other respiratory viruses were tested by molecular assays simultaneously. Data were analyzed to describe the frequency and seasonality. Of the 2025 children enrolled in the study, 971 (48.0%) were positive for at least one viral pathogen, in which 890 (91.7%) were respiratory syncytial virus (RSV; 30.5%) and human rhinovirus (HRV; 21.5%). Co-infections were found in 302 cases (31.1%), and dual viral infection was dominant. RSV, HRV and IAV were the most frequent viral agents involved in co-infection. On the whole, the obvious seasonal peaks mainly from March to May were observed with peak strength varying from 1 year to another. This study provides a basic profile of the epidemiology of acute respiratory viral infection in hospitalized children in Shenzhen. The spectrum of viruses in the study site is similar to that in other places, but the seasonality is closely related to geographic position, different from that in big cities in northern China and neighboring Hong Kong. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  19. The role of Mycobacterium avium complex fibronectin attachment protein in adherence to the human respiratory mucosa.

    Science.gov (United States)

    Middleton, A M; Chadwick, M V; Nicholson, A G; Dewar, A; Groger, R K; Brown, E J; Wilson, R

    2000-10-01

    Mycobacterium avium complex (MAC) are opportunistic respiratory pathogens that infect non-immunocompromised patients with established lung disease, although they can also cause primary infections. The ability to bind fibronectin is conserved among many mycobacterial species. We have investigated the adherence of a sputum isolate of MAC to the mucosa of organ cultures constructed with human tissue and the contribution of M. avium fibronectin attachment protein (FAP) to the process. MAC adhered to fibrous, but not globular mucus, and to extracellular matrix (ECM) in areas of epithelial damage, but not to intact extruded cells and collagen fibres. Bacteria occasionally adhered to healthy unciliated epithelium and to cells that had degenerated exposing their contents, but never to ciliated cells. The results obtained with different respiratory tissues were similar. Two ATCC strains of MAC gave similar results. There was a significant reduction (P fibrous mucus was unchanged. Immunogold labelling demonstrated fibronectin in ECM as well as in other areas of epithelial damage, but only ECM bound FAP. A Mycobacterium smegmatis strain had the same pattern of adherence to the mucosa as MAC. When the FAP gene was deleted, the strain demonstrated reduced adherence to ECM, and adherence was restored when the strain was transfected with an M. avium FAP expression construct. We conclude that MAC adheres to ECM in areas of epithelial damage via FAP and to mucus with a fibrous appearance via another adhesin. Epithelial damage exposing ECM and poor mucus clearance will predispose to MAC airway infection.

  20. Testing Human Skin and Respiratory Sensitizers—What Is Good Enough?

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    Anki Malmborg

    2017-01-01

    Full Text Available Alternative methods for accurate in vitro assessment of skin and respiratory sensitizers are urgently needed. Sensitization is a complex biological process that cannot be evaluated accurately using single events or biomarkers, since the information content is too restricted in these measurements. On the contrary, if the tremendous information content harbored in DNA/mRNA could be mined, most complex biological processes could be elucidated. Genomic technologies available today, including transcriptional profiling and next generation sequencing, have the power to decipher sensitization, when used in the right context. Thus, a genomic test platform has been developed, denoted the Genomic Allergen Rapid Detection (GARD assay. Due to the high informational content of the GARD test, accurate predictions of both the skin and respiratory sensitizing capacity of chemicals, have been demonstrated. Based on a matured dendritic cell line, acting as a human-like reporter system, information about potency has also been acquired. Consequently, multiparametric diagnostic technologies are disruptive test principles that can change the way in which the next generation of alternative methods are designed.

  1. Effects of respiratory alkalosis on human skeletal muscle metabolism at the onset of submaximal exercise.

    Science.gov (United States)

    LeBlanc, P J; Parolin, M L; Jones, N L; Heigenhauser, G J F

    2002-10-01

    The purpose of this study was to examine the effects of respiratory alkalosis on human skeletal muscle metabolism at rest and during submaximal exercise. Subjects exercised on two occasions for 15 min at 55 % of their maximal oxygen uptake while either hyperventilating (R-Alk) or breathing normally (Con). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to R-Alk. In the first minute of exercise, there was a delayed activation of pyruvate dehydrogenase (PDH) in R-Alk compared with Con, resulting in a reduced rate of pyruvate oxidation. Also, glycogenolysis was higher in R-Alk compared with Con, which was attributed to a higher availability of the monoprotonated form of inorganic phosphate (P(i)), resulting in an elevated rate of pyruvate production. The mismatch between pyruvate production and its oxidation resulted in net lactate accumulation. These effects were not seen after 15 min of exercise, with no further differences in muscle metabolism between conditions. The results from the present study suggest that respiratory alkalosis may play an important role in lactate accumulation during the transition from rest to exercise in acute hypoxic conditions, but that other factors mediate lactate accumulation during steady-state exercise.

  2. Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium.

    Science.gov (United States)

    Amitani, R; Taylor, G; Elezis, E N; Llewellyn-Jones, C; Mitchell, J; Kuze, F; Cole, P J; Wilson, R

    1995-09-01

    The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways.

  3. [Different species of human rhinovirus infection in children with acute respiratory tract infections in Beijing].

    Science.gov (United States)

    Song, Ming-hui; Zhao, Lin-qing; Qian, Yuan; Zhu, Ru-nan; Deng, Jie; Wang, Fang; Sun, Yu; Tian, Run

    2013-12-01

    To understand the clinical characteristics of different groups human rhinovirus (HRV)-A, B and C infection in children with acute respiratory tract infections (ARI) in Beijing. Respiratory tract specimens (n = 1412) collected from children with ARI during Jan. 2011 to Dec. 2012 were tested for HRV by using semi-nested PCR. Gene fragments of VP4/VP2 capsid protein amplified from HRV positive specimens were sequenced for HRV genotype confirmation. Then epidemiological characteristics of these HRV-positive cases were analyzed. Among these 1412 specimens tested, 103 (7.3%) were HRV positive, including 54 (52.4%) positive for HRV-A, 14 (13.6%) for HRV-B, 35 (34.0%) for HRV-C determined by sequence analysis. The positive rates of HRV-A, B and C (2.5%, 16/638; 0.3%, 2/638 and 1.3%, 8/638) in children with acute upper respiratory tract infections (URI) were lower than those (5.8%, 36/623; 1.8%, 11/623 and 3.9%, 24/623) in children with acute lower respiratory tract infections (LRI) (P = 0.003, 0.011, 0.003). In children with LRI, the positive rates of HRV-A, C were similar to each other (P = 0.112), and both were higher than that of HRV-B (P = 0.000, P = 0.026). The severity of ARI among children positive for different groups HRV showed no significant difference evaluated by Kruskal-Wallis H test (Hc = 0.044, P > 0.05), as well as that between children co-infected with HRV and other viruses and those infected with HRV only evaluated by Wilcoxon rank sum test (Zc = 0.872, P > 0.05). HRV is one of important pathogens for children with ARI, especially LRI in Beijing. The positive rates of HRV-A and HRV-C are similar to each other, and both are higher than that of HRV-B. No significant difference was shown among children with different HRV genotypes by evaluation of the severity of ARI, and co-infections of HRV with other viruses do not significantly increase the severity of ARI.

  4. Glycolipid-Dependent, Protease Sensitive Internalization of Pseudomonas aeruginosa Into Cultured Human Respiratory Epithelial Cells

    Science.gov (United States)

    Emam, Aufaugh; Carter, William G; Lingwood, Clifford

    2010-01-01

    Internalization of PAK strain Pseudomonas aeruginosa into human respiratory epithelial cell lines and HeLa cervical cancer cells in vitro was readily demonstrable via a gentamycin protection assay. Depletion of target cell glycosphingolipids (GSLs) using a glucosyl ceramide synthase inhibitor, P4, completely prevented P. aeruginosa internalization. In contrast, P4 treatment had no effect on the internalization of Salmonella typhimurium into HeLa cells. Internalized P. aeruginosa were within membrane vacuoles, often containing microvesicles, between the bacterium and the limiting membrane. P. aeruginosa internalization was markedly enhanced by target cell pretreatment with the exogenous GSL, deacetyl gangliotetraosyl ceramide (Gg4). Gg4 binds the lipid raft marker, GM1 ganglioside. Target cell pretreatment with TLCK, but not other (serine) protease inhibitors, prevented both P. aeruginosa host cell binding and internalization. NFkB inhibition also prevented internalization. A GSL-containing lipid-raft model of P. aeruginosa host cell binding/internalization is proposed PMID:21270937

  5. The potential health and economic benefits of preventing recurrent respiratory papillomatosis through quadrivalent human papillomavirus vaccination.

    Science.gov (United States)

    Chesson, Harrell W; Forhan, Sara E; Gottlieb, Sami L; Markowitz, Lauri E

    2008-08-18

    We estimated the health and economic benefits of preventing recurrent respiratory papillomatosis (RRP) through quadrivalent human papillomavirus (HPV) vaccination. We applied a simple mathematical model to estimate the averted costs and quality-adjusted life years (QALYs) saved by preventing RRP in children whose mothers had been vaccinated at age 12 years. Under base case assumptions, the prevention of RRP would avert an estimated USD 31 (range: USD 2-178) in medical costs (2006 US dollars) and save 0.00016 QALYs (range: 0.00001-0.00152) per 12-year-old girl vaccinated. Including the benefits of RRP reduced the estimated cost per QALY gained by HPV vaccination by roughly 14-21% in the base case and by 100% in the sensitivity analyses. More precise estimates of the incidence of RRP are needed, however, to quantify this impact more reliably.

  6. Practical application of the new ICRP Human Respiratory Tract Model (invited paper)

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, M.R.; Guilmette, R.A.; Jarvis, N.S.; Roy, M

    1998-07-01

    The ICRP Publication 66 Human Respiratory Tract Model (HRTM) has been applied to calculate general-purpose dose coefficients using default values of parameters relating to the material and the subjects. The ICRP Task Group on Internal Dosimetry is developing a 'Technical Document' giving guidance on application of the HRTM in situations where using specific information can improve dose assessment. It will include an analysis of the sensitivity of doses and bioassay quantities, lung retention and excretion rates, to relevant parameter values. Guidance will be given on characterising and sampling radioactive aerosols and on determining absorption rates. Examples will be given illustrating application of the HRTM in a wide range of situations. This paper provides a selective summary of the document at its current stage of development, with emphasis on determining absorption rates. (author)

  7. Etiology of acute lower respiratory tract infections in children: current state of the issue (review

    Directory of Open Access Journals (Sweden)

    A. V. Bogdanova

    2016-01-01

    Full Text Available Acute lower respiratory tract infections are the leading cause of global morbidity and mortality in children under five years. Verification of the etiology of acute lower respiratory tract infections is necessary for definition of treatment and direction of prevention. Respiratory syncytial virus, influenza A and B, parainfluenza 1, 2, and 3 and adenovirus are considered the main reasons of acute lower respiratory tract infections. The importance of different viruses depends on countries, district, seasons and ages of children. Analysis of the results of studies from different regions of the world showed fluctuations in frequency of etiology definition of respiratory viruses from 25 to 90%. Respiratory syncytial virus is the main reason of acute lower respiratory tract infections, especially in the group of children up to 1 year.

  8. High prevalence of common respiratory viruses and no evidence of Middle East respiratory syndrome coronavirus in Hajj pilgrims returning to Ghana, 2013.

    Science.gov (United States)

    Annan, Augustina; Owusu, Michael; Marfo, Kwadwo Sarfo; Larbi, Richard; Sarpong, Francisca Naana; Adu-Sarkodie, Yaw; Amankwa, Joseph; Fiafemetsi, Samuel; Drosten, Christian; Owusu-Dabo, Ellis; Eckerle, Isabella

    2015-06-01

    The Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 on the Arabian Peninsula and has caused severe respiratory disease with more than 800 laboratory-confirmed cases. The return of infected pilgrims to their home countries with a putative spread of MERS-CoV necessitates further surveillance. A cross sectional study of 839 adult African Hajj pilgrims returning to Accra in Ghana, West Africa, was conducted in 2013 to assess the prevalence of respiratory symptoms as well as of MERS-CoV, human rhinovirus (HRV), respiratory syncytial virus (RSV) and influenza A virus (FLU A) infection. Six hundred and fifty-one (77.6%) pilgrims had respiratory symptoms. Tests were positive for at least one of the viruses other than MERS-CoV in 179 (21.3%) of all pilgrims, with 22.4% detection in symptomatic vs. 17.6% detection in asymptomatic pilgrims. No MERS-CoV was detected, although common respiratory viruses were prevalent, with positive findings for HRV in 141 individuals (16.8%), RSV in 43 individuals (5.1%) and FLU A in 11 individuals (1.3%). Results were positive for more than one virus in 16 (1.9%) individuals, including 14 (1.7%) RSV/HRV co-infections and 2 (0.2%) FLU A/HRV co-infections. A total 146 (22.4%) of the symptomatic returnees tested positive for at least one respiratory virus compared with 33 (17.6%) of the asymptomatic pilgrims who had at least one detectable virus in their sample. The prevalence of viral respiratory infections among Hajj pilgrims in both symptomatic and asymptomatic subjects was high. Although it is reassuring that MERS-CoV was not detected in the tested population, there is a need for active surveillance of Hajj pilgrims. © 2015 John Wiley & Sons Ltd.

  9. Osmolality and respiratory regulation in humans: respiratory compensation for hyperchloremic metabolic acidosis is absent after infusion of hypertonic saline in healthy volunteers.

    Science.gov (United States)

    Moen, Vibeke; Brudin, Lars; Rundgren, Mats; Irestedt, Lars

    2014-10-01

    Several animal studies show that changes in plasma osmolality may influence ventilation. Respiratory depression caused by increased plasma osmolality is interpreted as inhibition of water-dependent thermoregulation because conservation of body fluid predominates at the cost of increased core temperature. Respiratory alkalosis, on the other hand, is associated with a decrease in plasma osmolality and strong ion difference (SID) during human pregnancy. We investigated the hypothesis that osmolality would influence ventilation, so that increased osmolality will decrease ventilation and decreased osmolality will stimulate ventilation in both men and women. Our study participants were healthy volunteers of both sexes (ASA physical status I). Ten men (mean 28 years; range 20-40) and 9 women (mean 33 years; range 22-43) were included. All women participated in both the follicular and luteal phases of the menstrual cycle. Hyperosmolality was induced by IV infusion of hypertonic saline 3%, and hypoosmolality by drinking tap water. Arterial blood samples were collected for analysis of electrolytes, osmolality, and blood gases. Sensitivity to CO2 was determined by rebreathing tests performed before and after the fluid-loading procedures. Infusion of hypertonic saline caused hyperchloremic metabolic acidosis with decreased SID in all subjects. Analysis of pooled data showed absence of respiratory compensation. Baseline arterial PCO2 (PaCO2) mean (SD) 37.8 (2.9) mm Hg remained unaltered, with lowest PaCO2 37.8 (2.9) mm Hg after 100 minutes, P = 0.70, causing a decrease in pH from mean (SD) 7.42 (0.02) to 7.38 (0.02), P acidosis was also observed during water loading. Pooled results show that PaCO2 decreased from 38.2 (3.3) mm Hg at baseline to 35.7 (2.8) mm Hg after 80 minutes of drinking water, P = 0.002, and pH remained unaltered: pH 7.43 (0.02) at baseline to pH 7.42 (0.02), P = 0.14, mean difference (confidence interval) = pH -0.007 (-0.017 to 0.003). Our results indicate

  10. Morphological changes of carotid bodies in acute respiratory distress syndrome: a morphometric study in humans

    Directory of Open Access Journals (Sweden)

    Vinhaes E.N.G.

    2002-01-01

    Full Text Available Carotid bodies are chemoreceptors sensitive to a fall of partial oxygen pressure in blood (hypoxia. The morphological alterations of these organs in patients with chronic obstructive pulmonary disease (COPD and in people living at high altitude are well known. However, it is not known whether the histological profile of human carotid bodies is changed in acute clinical conditions such as acute respiratory distress syndrome (ARDS. The objective of the present study was to perform a quantitative analysis of the histology of carotid bodies collected from patients who died of ARDS. A morphometric study of carotid bodies collected during routine autopsies was carried out on three groups: patients that died of non-respiratory diseases (controls, N = 8, patients that presented COPD and died of its complications or associated diseases (N = 7, and patients that died of ARDS (N = 7. Morphometric measurements of the volume fraction of clusters of chief cells were performed in five fields on each slide at 40X magnification. The numerical proportion of the four main histological cell types (light, dark, progenitor and sustentacular cells was determined analyzing 10 fields on each slide at 400X magnification. The proportion of dark cells was 0.22 in ARDS patients, 0.12 in controls (P<0.001, and 0.08 in the COPD group. The proportion of light cells was 0.33 (ARDS, 0.44 (controls (P<0.001, and 0.36 (COPD. These findings suggest that chronic and acute hypoxia have different effects on the histology of glomic tissue.

  11. Mycobacterium talmoniae sp. nov., a slowly growing mycobacterium isolated from human respiratory samples.

    Science.gov (United States)

    Davidson, Rebecca M; DeGroote, Mary Ann; Marola, Jamie L; Buss, Sarah; Jones, Victoria; McNeil, Michael R; Freifeld, Alison G; Elaine Epperson, L; Hasan, Nabeeh A; Jackson, Mary; Iwen, Peter C; Salfinger, Max; Strong, Michael

    2017-08-01

    A novel slowly growing, non-chromogenic species of the class Actinobacteria was isolated from a human respiratory sample in Nebraska, USA, in 2012. Analysis of the internal transcribed spacer sequence supported placement into the genus Mycobacterium with high sequence similarity to a previously undescribed strain isolated from a patient respiratory sample from Oregon, USA, held in a collection in Colorado, USA, in 2000. The two isolates were subjected to phenotypic testing and whole genome sequencing and found to be indistinguishable. The bacteria were acid-fast stain-positive, rod-shaped and exhibited growth after 7-10 days on solid media at temperatures ranging from 25 to 42°C. Colonies were non-pigmented, rough and slightly raised. Analyses of matrix-assisted laser desorption ionization time-of-flight profiles showed no matches against a reference library of 130 mycobacterial species. Full-length 16S rRNA gene sequences were identical for the two isolates, the average nucleotide identity (ANI) between their genomes was 99.7 % and phylogenetic comparisons classified the novel mycobacteria as the basal most species in the slowly growing Mycobacterium clade. Mycobacterium avium is the most closely related species based on rpoB gene sequence similarity (92 %), but the ANI between the genomes was 81.5 %, below the suggested cut-off for differentiating two species (95 %). Mycolic acid profiles were more similar to M. avium than to Mycobacterium simiae or Mycobacterium abscessus. The phenotypic and genomic data support the conclusion that the two related isolates represent a novel Mycobacterium species for which the name Mycobacterium talmoniae sp. nov. is proposed. The type strain is NE-TNMC-100812T (=ATCC BAA-2683T=DSM 46873T).

  12. Deposition of biomass combustion aerosol particles in the human respiratory tract.

    Science.gov (United States)

    Löndahl, Jakob; Pagels, Joakim; Boman, Christoffer; Swietlicki, Erik; Massling, Andreas; Rissler, Jenny; Blomberg, Anders; Bohgard, Mats; Sandström, Thomas

    2008-08-01

    Smoke from biomass combustion has been identified as a major environmental risk factor associated with adverse health effects globally. Deposition of the smoke particles in the lungs is a crucial factor for toxicological effects, but has not previously been studied experimentally. We investigated the size-dependent respiratory-tract deposition of aerosol particles from wood combustion in humans. Two combustion conditions were studied in a wood pellet burner: efficient ("complete") combustion and low-temperature (incomplete) combustion simulating "wood smoke." The size-dependent deposition fraction of 15-to 680-nm particles was measured for 10 healthy subjects with a novel setup. Both aerosols were extensively characterized with regard to chemical and physical particle properties. The deposition was additionally estimated with the ICRP model, modified for the determined aerosol properties, in order to validate the experiments and allow a generalization of the results. The measured total deposited fraction of particles from both efficient combustion and low-temperature combustion was 0.21-0.24 by number, surface, and mass. The deposition behavior can be explained by the size distributions of the particles and by their ability to grow by water uptake in the lungs, where the relative humidity is close to saturation. The experiments were in basic agreement with the model calculations. Our findings illustrate: (1) that particles from biomass combustion obtain a size in the respiratory tract at which the deposition probability is close to its minimum, (2) that particle water absorption has substantial impact on deposition, and (3) that deposition is markedly influenced by individual factors.

  13. El Bocavirus humano: un nuevo virus respiratorio Human bocavirus: a new respiratory virus

    Directory of Open Access Journals (Sweden)

    Carlos Aguirre Muñoz

    2006-01-01

    Full Text Available Las infecciones respiratorias agudas son una causa muy importante de morbilidad y mortalidad, especialmente en los niños y en los países en desarrollo. Con los métodos de laboratorio actuales, aproximadamente una tercera parte de estas infecciones se queda sin diagnóstico etiológico. Se acepta que los virus juegan un papel cardinal y que más de 200 virus, pertenecientes a seis familias virales están implicados en la génesis de este problema. La familia Parvoviridae se conoce desde mediados del siglo XX. El Parvovirus humano B19, identificado en 1980 y causante de enfermedades febriles y exantemáticas, fue considerado por muchos años como el único miembro de esta familia capaz de afectar a la especie humana. Sin embargo, un grupo de investigadores suecos comandado por Tobías Allander informó en agosto de 2005 el hallazgo de un nuevo Parvovirus, denominado provisionalmente Bocavirus humano, relacionado con infección respiratoria aguda en niños. En este artículo se resumen las características de este nuevo agente, se resalta la importancia de su hallazgo y de la técnica de investigación empleada. Respiratory tract infections are a leading cause of morbidity and mortality, mainly in children and also in developing countries. The aethiology of approximately 30% of these infections remains obscure, using current laboratory methods. It has been accepted that viruses play an important role and more than 200 viruses, belonging to 6 viral families are implied in the pathogenesis of this problem. Parvoviridae family has been known since the middle of the XX century. Human Parvovirus B19 was identified in 1980; it causes rashes and febrile diseases and it was considered for many years as the only member of this family able to affect humans. However, Dr. Tobias Allander and colleagues, at Karolinska Institut, have discovered a previously unknown parvovirus, called Human Bocavirus, that has been found to affect children, causing lower

  14. Identification of Burkholderia mallei and Burkholderia pseudomallei adhesins for human respiratory epithelial cells

    Directory of Open Access Journals (Sweden)

    Hogan Robert J

    2010-09-01

    Full Text Available Abstract Background Burkholderia pseudomallei and Burkholderia mallei cause the diseases melioidosis and glanders, respectively. A well-studied aspect of pathogenesis by these closely-related bacteria is their ability to invade and multiply within eukaryotic cells. In contrast, the means by which B. pseudomallei and B. mallei adhere to cells are poorly defined. The purpose of this study was to identify adherence factors expressed by these organisms. Results Comparative sequence analyses identified a gene product in the published genome of B. mallei strain ATCC23344 (locus # BMAA0649 that resembles the well-characterized Yersinia enterocolitica autotransporter adhesin YadA. The gene encoding this B. mallei protein, designated boaA, was expressed in Escherichia coli and shown to significantly increase adherence to human epithelial cell lines, specifically HEp2 (laryngeal cells and A549 (type II pneumocytes, as well as to cultures of normal human bronchial epithelium (NHBE. Consistent with these findings, disruption of the boaA gene in B. mallei ATCC23344 reduced adherence to all three cell types by ~50%. The genomes of the B. pseudomallei strains K96243 and DD503 were also found to contain boaA and inactivation of the gene in DD503 considerably decreased binding to monolayers of HEp2 and A549 cells and to NHBE cultures. A second YadA-like gene product highly similar to BoaA (65% identity was identified in the published genomic sequence of B. pseudomallei strain K96243 (locus # BPSL1705. The gene specifying this protein, termed boaB, appears to be B. pseudomallei-specific. Quantitative attachment assays demonstrated that recombinant E. coli expressing BoaB displayed greater binding to A549 pneumocytes, HEp2 cells and NHBE cultures. Moreover, a boaB mutant of B. pseudomallei DD503 showed decreased adherence to these respiratory cells. Additionally, a B. pseudomallei strain lacking expression of both boaA and boaB was impaired in its ability to

  15. Influence of a Gas Exchange Correction Procedure on Resting Metabolic Rate and Respiratory Quotient in Humans.

    Science.gov (United States)

    Galgani, Jose E; Castro-Sepulveda, Mauricio A

    2017-11-01

    The aim of this study was to determine the influence of a gas exchange correction protocol on resting metabolic rate (RMR) and respiratory quotient (RQ), assessed by a Vmax Encore 29n metabolic cart (SensorMedics Co., Yorba Linda, California) in overnight fasted and fed humans, and to assess the predictive power of body size for corrected and uncorrected RMR. Healthy participants (23 M/29 F; 34 ± 9 years old; 26.3 ± 3.7 kg/m 2 ) ingested two 3-hour-apart glucose loads (75 g). Indirect calorimetry was conducted before and hourly over a 6-hour period. Immediately after indirect calorimetry assessment, gas exchange was simulated through high-precision mass-flow regulators, which permitted the correction of RMR and RQ values. Uncorrected and corrected RMR and RQ were directly related at each time over the 6-hour period. However, uncorrected versus corrected RMR was 6.9% ± 0.5% higher (128 ± 7 kcal/d; P exchange in humans over a 6-hour period is feasible and provides information of improved accuracy. © 2017 The Obesity Society.

  16. Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kailang; Li, Weikai; Peng, Guiqing; Li, Fang; (Harvard-Med); (UMM-MED)

    2010-03-04

    NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel {beta}-sandwich core structure consisting of 2 layers of {beta}-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a 'virus-binding hotspot' on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions.

  17. Application of morphological and physiological parameters representative of a sample Brazilian population in the human respiratory tract model

    International Nuclear Information System (INIS)

    Reis, A.A.; Cardoso, J.C.S.; Lourenco, M.C.

    2005-01-01

    Full text: The Human Respiratory Tract Model (HRTM) proposed in ICRP Publication 66 account for the morphology and physiology of the respiratory tract. The characteristics of air drawn into the lungs and exhaled are greatly influenced by the morphology of the respiratory tract, which causes numerous changes in pressure, flow rate, direction and humidity as air moves into and out of the lungs. These changing characteristics can influence the rates and the sites of deposition. Concerning the respiratory physiological parameters the breathing characteristics influence the volume, the inhalation rate of air and the portion that enters through the nose and the mouth. These characteristics are important to determine the fractional deposition. The HRTM model uses morphological and physiological parameters from the Caucasian man to establish deposition fractions in the respiratory tract regions. lt is known that the morphology and physiology are influenced by environmental, occupational and economic conditions. The ICRP recommends for a reliable evaluation of the regional deposition the use of parameters from a local population when information is available. The main purpose of this study is to verify the influence in using the morphology and physiology parameters representative of a sample of the Brazilian population on the deposition model of ICRP Publication 66. The morphological and physiological data were obtained from the literature. The software EXCEL for Windows (version 2000) was used in order to implement the deposition model and also to allow the changes in parameters of interest. Initially, the implemented model was checked using the parameters defined in ICRP and the results of the fraction deposition in the respiratory tract compartments were compared. Finally, morphological and physiological parameters from Brazilian adult male were applied and the fractional deposition calculated. The respiratory values at different levels of activity for ages varying from

  18. Distance to human populations influences epidemiology of respiratory disease in desert tortoises

    Science.gov (United States)

    Berry, Kristin H.; Ashley A. Coble (formerly Emerson), no longer USGS; Yee, Julie L.; Mack, Jeremy S.; Perry, William M.; Anderson, Kemp M.; Brown, Mary B.

    2014-01-01

    We explored variables likely to affect health of Agassiz's desert tortoises (Gopherus agassizii) in a 1,183-km2 study area in the central Mojave Desert of California between 2005 and 2008. We evaluated 1,004 tortoises for prevalence and spatial distribution of 2 pathogens, Mycoplasma agassizii and M. testudineum, that cause upper respiratory tract disease. We defined tortoises as test-positive if they were positive by culture and/or DNA identification or positive or suspect for specific antibody for either of the two pathogens. We used covariates of habitat (vegetation, elevation, slope, and aspect), tortoise size and sex, distance from another test-positive tortoise, and anthropogenic variables (distances to roads, agricultural areas, playas, urban areas, and centroids of human-populated census blocks). We used both logistic regression models and regression trees to evaluate the 2 species of Mycoplasma separately. The prevalence of test-positive tortoises was low: 1.49% (15/1,004) for M. agassizii and 2.89% (29/1,004) for M. testudineum. The spatial distributions of test-positive tortoises for the 2 Mycoplasma species showed little overlap; only 2 tortoises were test-positive for both diseases. However, the spatial distributions did not differ statistically between the 2 species. We consistently found higher prevalence of test-positive tortoises with shorter distances to centroids of human-populated census blocks. The relationship between distance to human-populated census blocks and tortoises that are test-positive for M. agassizii and potentially M. testudineum may be related to release or escape of captive tortoises because the prevalence of M. agassizii in captive tortoises is high. Our findings have application to other species of chelonians where both domestic captive and wild populations exist. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  19. RSV-induced bronchiolitis but not upper respiratory tract infection is accompanied by an increased nasal IL-18 response

    NARCIS (Netherlands)

    van Benten, Inesz J.; van Drunen, Cornelis M.; Koopman, Laurens P.; Kleinjan, Alex; van Middelkoop, Barbara C.; de Waal, Leon; Osterhaus, Albert D. M. E.; Neijens, Herman J.; Fokkens, Wytske J.

    2003-01-01

    The aim of this study was to investigate potential differences in the local nasal immune response between bronchiolitis and upper respiratory tract infection induced by respiratory syncytial virus (RSV). Nasal brush samples were obtained from 14 infants with RSV bronchiolitis and from 8 infants with

  20. Burden and Seasonality of Viral Acute Respiratory Tract Infections among Outpatients in Southern Sri Lanka.

    Science.gov (United States)

    Shapiro, David; Bodinayake, Champica K; Nagahawatte, Ajith; Devasiri, Vasantha; Kurukulasooriya, Ruvini; Hsiang, Jeremy; Nicholson, Bradley; De Silva, Aruna Dharshan; Østbye, Truls; Reller, Megan E; Woods, Christopher W; Tillekeratne, L Gayani

    2017-07-01

    In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses. Monthly proportion positive was calculated for each virus. Bivariable and multivariable logistic regression were used to identify associations between sociodemographic/clinical information and viral detection. Of 571 subjects, most (470, 82.3%) were ≥ 5 years of age and 53.1% were male. A respiratory virus was detected by PCR in 63.6% ( N = 363). Common viral etiologies included influenza (223, 39%), human enterovirus/rhinovirus (HEV/HRV, 14.5%), respiratory syncytial virus (RSV, 4.2%), and human metapneumovirus (hMPV, 3.9%). Both ILI and influenza showed clear seasonal variation, with peaks from March to June each year. RSV and hMPV activity peaked from May to July, whereas HEV/HRV was seen year-round. Patients with respiratory viruses detected were more likely to report pain with breathing (odds ratio [OR] = 2.60, P = 0.003), anorexia (OR = 2.29, P respiratory viruses detected. ILI showed clear seasonal variation in southern Sri Lanka, with most activity during March to June; peak activity was largely due to influenza. Targeted infection prevention activities such as influenza vaccination in January-February may have a large public health impact in this region.

  1. Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Mary K. McCarthy

    2012-01-01

    Full Text Available Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection.

  2. Blood flow index using near-infrared spectroscopy and indocyanine green as a minimally invasive tool to assess respiratory muscle blood flow in humans

    DEFF Research Database (Denmark)

    Guenette, Jordan A; Henderson, William R; Dominelli, Paolo B

    2011-01-01

    Near-infrared spectroscopy (NIRS) in combination with indocyanine green (ICG) dye has recently been used to measure respiratory muscle blood flow (RMBF) in humans. This method is based on the Fick principle and is determined by measuring ICG in the respiratory muscles using transcutaneous NIRS...... relationships with the work of breathing and EMG for both respiratory muscles. The coefficients of determination (R(2)) comparing BFI vs. the work of breathing for the intercostal and sternocleidomastoid muscles were 0.887 (P

  3. A mathematical model of transport and regional uptake of radioactive gases in the human respiratory system

    Science.gov (United States)

    Baek, Inseok

    The purpose of this research is to describe the development of a mathematical model of diffusion, convection, and lateral transport into the airway wall and alveolar absorption for inhaled radioactive gases in the human conductive and respiratory airways based on a Single Path Trumpet-bell model (SPM). Mathematical simulation models have been used successfully to study transport, absorption into the blood through alveoli, and lung tissue uptake of soluble and nonreactive radioactive gases. Results from such simulations also show clearly that inhaled radioactive gases are absorbed into the lung tissues as well as into the blood through the alveoli. In contrast to previous reports in the literature, the present study found that blood uptake through alveoli is much greater than that calculated previously. Regional depositions in the lung from inhaled radioactive gases are presented as the result of this simulation. The committed effective dose to lung tissue due to submersion in radioactive clouds has been newly defined using the results of this simulation.

  4. [Detection and Analysis of Human Parainfluenza Virus Infection in Hospitalized Adults with Acute Respiratory Tract Infections].

    Science.gov (United States)

    Li, Xing-Qiao; Liu, Xue-Wei; Zhou, Tao; Pei, Xiao-Fang

    2017-11-01

    To investigate the prevalence and gene characteristics of different groups of human parainfluenza virus (HPIV) infection in hospitalized adults with acute respiratory tract infections (ARI). RT-PCR was used to detect HPIV hemagglutinin (HA) DNA,which was extracted from sputum samples of 1 039 adult patients with ARI from March,2014 to June,2016. The HA gene amplified from randomly selected positive samples were sequenced to analyze the homology and variation. 10.6% (110/1 039) of these samples were positive for HPIV,including 8 cases of HPIV-1,22 cases of HPIV-2,46 cases of HPIV-3 and 34 cases of HPIV-4. Detectable rate varied among different groups of HPIV according to seasons of the year and ages of patients. No significant differences were found between the positive samples and the reference sequences. Compared with different reference strains of different regions,the genetic distance of nucleotide is the smallest between the strains tested in this study and the reference strains of other provinces and cities in China. In Chengdu region,HPIV virus is highly detected in ARI,all subtypes were detected with HPIV-3 being the main subtype.

  5. Human nasal turbinates as a viable source of respiratory epithelial cells using co-culture system versus dispase-dissociation technique.

    Science.gov (United States)

    Noruddin, Nur Adelina Ahmad; Saim, Aminuddin B; Chua, Kien Hui; Idrus, Ruszymah

    2007-12-01

    To compare a co-culture system with a conventional dispase-dissociation method for obtaining functional human respiratory epithelial cells from the nasal turbinates for tissue engineering application. Human respiratory epithelial cells were serially passaged using a co-culture system and a conventional dispase-dissociation technique. The growth kinetics and gene expression levels of the cultured respiratory epithelial cells were compared. Four genes were investigated, namely cytokeratin-18, a marker for ciliated and secretory epithelial cells; cytokeratin-14, a marker for basal epithelial cells; MKI67, a proliferation marker; and MUC5B, a marker for mucin secretion. Immunocytochemical analysis was performed using monoclonal antibodies against the high molecular-weight cytokeratin 34 beta E12, cytokeratin 18, and MUC5A to investigate the protein expression from cultured respiratory epithelial cells. Respiratory epithelial cells cultured using both methods maintained polygonal morphology throughout the passages. At passage 1, co-cultured respiratory epithelial showed a 2.6-times higher growth rate compared to conventional dispase dissociation technique, and 7.8 times higher at passage 2. Better basal gene expression was observed by co-cultured respiratory epithelial cells compared to dispase dissociated cells. Immunocytochemical analyses were positive for the respiratory epithelial cells cultured using both techniques. Co-culture system produced superior quality of cultured human respiratory epithelial cells from the nasal turbinates as compared to dispase dissociation technique.

  6. The revised International Commission on Radiological Protection (ICRP) dosimetric model for the human respiratory tract

    International Nuclear Information System (INIS)

    Bair, W.J.

    1992-05-01

    A task group has revised the dosimetric model of the respiratory tract used to calculate annual limits on intake of radionuclides. The revised model can be used to project respiratory tract doses for workers and members of the public from airborne radionuclides and to assess past exposures. Doses calculated for specific extrathoracic and thoracic tissues can be adjusted to account for differences in radiosensitivity and summed to yield two values of dose for the respiratory tract that are applicable to the ICRP tissue weighted dosimetry system

  7. Prevalence of Human Papillomavirus (HPV in upper respiratory tract mucosa in a group of pre-school children

    Directory of Open Access Journals (Sweden)

    Jaroslaw Szydłowski

    2014-11-01

    Full Text Available [b]introduction[/b]. Human Papillomavirus (HPV is a group of DNA viruses which is an etiological factor of many benign and malignant diseases of the upper respiratory tract mucosa, female genital tract and the skin. HPV infection is considered a sexually-transmitted infection, but can also be transmitted by non-sexual routes, including perinatal vertical transmission, physical contact, iatrogenic infection and autoinoculation. Recurrent Respiratory Papillomatosis (RRP in children is connected with HPV infection transmitted vertically from mother to child during the passage of the foetus through an infected birth canal. [b]objective. [/b]The aim of this study was to establish the level of Human Papillomaviruses carrier state in upper respiratory tract mucosa in healthy pre-school children, and to identify potential risk factors for HPV infection. [b]materials and method[/b]. After obtaining consent from their parents, 97 pre-school children were examined – 51 girls and 46 boys between the ages of 3 – 5 years; average age – 4 years and 5 months. 68 children were urban dwellers and 29 came from a rural environment. A questionnaire with detailed history was taken including parents’ and child`s personal data, as well as perinatal risk factors in pregnancy. Socio-demographic information was also obtained, including the standard of living, and chosen environmental factors. Routine ENT examination was performed. Exfoliated oral squamous cells were collected from swabs and analysed for the presence of DNA papillomaviruses by polymerase chain reaction. [b]results.[/b] The presence of HPV in the respiratory tract in children was detected in 19.6% cases. ‘High oncogenic potential’ HPVs, such as HPV-16 and HPV-18, were not observed in squamous cell mucosa of the respiratory tract in the children. No significant differences were observed between the HPV carrier state in urban and rural inhabitants.

  8. Sequence analysis of the G gene of hRSVA ON1 genotype from Egyptian children with acute respiratory tract infections.

    Science.gov (United States)

    Abdel-Moneim, Ahmed S; Soliman, May S; Kamel, Mahmoud M; El-Kholy, Amani A

    2018-03-01

    Human respiratory syncytial virus causes severe lower respiratory tract infection in neonates and children. Genotype ON1, with duplication of 72-nt in the G gene, was first detected in Canada and then recorded in other countries. In the current study, we describe the first detection of the ON1 genotype among children in Egypt in 2014/2015. Sequence analysis of the full-attachment G gene revealed that the majority of the strains examined were related to the ON1 genotype and only one sample related to N1 genotype. The Egyptian ON1 strains showed unique non-silent mutations in addition to variable mutations near the antigenic sites in comparison to the original ON1 ancestor strain. Continuous surveillance of hRSV regionally and globally is needed to understand the evolutionary mechanisms and strategies adopted by hRSV and their inducers for better adaption to the host.

  9. Anti-virus effect of traditional Chinese medicine Yi-Fu-Qing granule on acute respiratory tract infections.

    Science.gov (United States)

    Li, Anyuan; Xie, Yanying; Qi, Fanghua; Li, Jie; Wang, Peng; Xu, Shulan; Zhao, Lin

    2009-08-01

    Yi-Fu-Qing granule is a traditional Chinese medicine for the treatment of acute respiratory tract infections. The present study sought to investigate the anti-virus effects of Yi-Fu-Qing granule on acute respiratory infections with respiratory syncytial virus (RSV) and human adenoviruses type 3 (Ad3). The cytotoxicity of Yi-Fu-Qing granule was evaluated by the neutral red assay on HeLa cells. The antiviral effect of Yi-Fu-Qing granule was tested by observing the cytopathogenic effect (CPE) with a compound mixture of Isatis leaf as the positive control drug. The results indicated that the highest non-toxicity concentration of Yi-Fu-Qing granule on Hela cells was 1:100. The CPE reduction assay showed that Yi-Fu-Qing granule inhibited RSV and Ad3 replication at a concentration of 1:100. Thus, Yi-Fu-Qing granule may have a significant antivirus effect on acute respiratory tract infections with RSV and Ad3 infections and this could prove useful for further antivirus research on acute respiratory tract infections.

  10. A Cross-sectional Surveillance Study of the Frequency and Etiology of Acute Respiratory Illness Among Pregnant Women.

    Science.gov (United States)

    Hause, Anne M; Avadhanula, Vasanthi; Maccato, Maurizio L; Pinell, Phillip M; Bond, Nanette; Santarcangelo, Patricia; Ferlic-Stark, Laura; Munoz, Flor M; Piedra, Pedro A

    2018-05-05

    Other than influenza, little is known about the consequences of viral acute respiratory illness (ARI) on pregnant women and fetuses. Our objectives were to determine the frequency of ARI due to respiratory viruses and the associated clinical outcomes during pregnancy. Pregnant women in their second or third trimester were enrolled if they reported having symptoms of ARI or were healthy within the preceding 2 weeks. Nasopharyngeal secretions were evaluated for respiratory viruses by molecular diagnostic assays. Clinical outcomes were evaluated at enrollment and via a follow-up telephone-based questionnaire 2 weeks later. There were 155 pregnant participants, with 81 ARI cases and 91 healthy controls. Acute lower respiratory tract illness (ALRTI) was identified in 29 cases (36%). Human rhinovirus (HRV), respiratory syncytial virus (RSV), and influenza virus accounted for 75% of virus-positive cases of ALRTI. Cases with ALRTI often reported a longer duration of illness, history of allergies, symptoms of wheezing, shortness of breath, or chest pain, and use of prescription medication. Two cases with ALRTI reported decreased fetal movement; a third case with ALRTI was hospitalized. In over one third of ARI cases, participants had symptoms consistent with ALRTI. Infection with HRV, RSV, or influenza virus was commonly detected in patients with ALRTI. Viral ALRTI during pregnancy appears to be common and is associated with significant morbidity.

  11. Early consumption of human milk oligosaccharides is inversely related to subsequent risk of respiratory and enteric disease in infants.

    Science.gov (United States)

    Stepans, Mary Beth Flanders; Wilhelm, Susan L; Hertzog, Melody; Rodehorst, T Kim Callahan; Blaney, Susan; Clemens, Beth; Polak, Josef J; Newburg, David S

    2006-01-01

    A pilot study tested the relationship between human milk oligosaccharide consumption, oligosaccharide content of feces, and subsequent disease in breastfed infants. Forty-nine (49) mother-infant pairs provided milk and fecal samples 2 weeks postpartum; infant health was assessed through 2, 6, 12, and 24 weeks. LNF-II (lacto-N-fucopentaose II), a major human milk oligosaccharide, was measured to represent levels of total oligosaccharides consumed in milk and remaining in feces. LNF-II levels in milk at 2 weeks postpartum were associated with fewer infant respiratory problems by 6 weeks (p = 0.010), as were LNF-II levels in infant feces (p = 0.003). LNF-II levels in milk at 2 weeks were also associated with fewer respiratory problems by 12 weeks (p = 0.038), and fewer enteric problems by 6 weeks (p = 0.004) and 12 weeks (p = 0.045). Thus, consumption of human milk oligosaccharides through breastfeeding, represented by LNF-II, was associated with less reported respiratory and gastrointestinal illness in infants.

  12. MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.

    Science.gov (United States)

    Baruffini, Enrico; Dallabona, Cristina; Invernizzi, Federica; Yarham, John W; Melchionda, Laura; Blakely, Emma L; Lamantea, Eleonora; Donnini, Claudia; Santra, Saikat; Vijayaraghavan, Suresh; Roper, Helen P; Burlina, Alberto; Kopajtich, Robert; Walther, Anett; Strom, Tim M; Haack, Tobias B; Prokisch, Holger; Taylor, Robert W; Ferrero, Ileana; Zeviani, Massimo; Ghezzi, Daniele

    2013-11-01

    We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype. © 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.

  13. Respiratory acidosis

    Science.gov (United States)

    Ventilatory failure; Respiratory failure; Acidosis - respiratory ... Causes of respiratory acidosis include: Diseases of the airways (such as asthma and COPD ) Diseases of the lung tissue (such as ...

  14. Real-world comparison of two molecular methods for detection of respiratory viruses

    Directory of Open Access Journals (Sweden)

    Miller E Kathryn

    2011-06-01

    Full Text Available Abstract Background Molecular polymerase chain reaction (PCR based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories. Methods We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA] and individual real-time RT-PCR (RT-rtPCR. Results Both assays detected viruses in more than 70% of specimens, but there was discordance. The RMA assay detected significantly more human metapneumovirus (HMPV and respiratory syncytial virus (RSV, while RT-rtPCR detected significantly more influenza A. We speculated that primer differences accounted for these discrepancies and redesigned the primers and probes for influenza A in the RMA assay, and for HMPV and RSV in the RT-rtPCR assay. The tests were then repeated and again compared. The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but the RMA assay remained similar in terms of influenza detection. Conclusions Given the absence of a gold standard, clinical and research laboratories should regularly correlate the results of molecular assays with other PCR based assays, other laboratories, and with standard virologic methods to ensure consistency and accuracy.

  15. A new laboratory-based surveillance system (Respiratory DataMart System) for influenza and other respiratory viruses in England: results and experience from 2009 to 2012.

    Science.gov (United States)

    Zhao, H; Green, H; Lackenby, A; Donati, M; Ellis, J; Thompson, C; Bermingham, A; Field, J; Sebastianpillai, P; Zambon, M; Watson, Jm; Pebody, R

    2014-01-23

    During the 2009 influenza A(H1N1) pandemic, a new laboratory-based virological sentinel surveillance system, the Respiratory DataMart System (RDMS), was established in a network of 14 Health Protection Agency (now Public Health England (PHE)) and National Health Service (NHS) laboratories in England. Laboratory results (both positive and negative) were systematically collected from all routinely tested clinical respiratory samples for a range of respiratory viruses including influenza, respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus, adenovirus and human metapneumovirus (hMPV). The RDMS also monitored the occurrence of antiviral resistance of influenza viruses. Data from the RDMS for the 2009–2012 period showed that the 2009 pandemic influenza virus caused three waves of activity with different intensities during the pandemic and post pandemic periods. Peaks in influenza A(H1N1)pdm09 positivity (defined as number of positive samples per total number of samples tested) were seen in summer and autumn in 2009, with slightly higher peak positivity observed in the first post-pandemic season in 2010/2011. The influenza A(H1N1)pdm09 virus strain almost completely disappeared in the second postpandemic season in 2011/2012. The RDMS findings are consistent with other existing community-based virological and clinical surveillance systems. With a large sample size, this new system provides a robust supplementary mechanism, through the collection of routinely available laboratory data at minimum extra cost, to monitor influenza as well as other respiratory virus activity. A near real-time, d