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Sample records for bovine respiratory syncytial

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

    DEFF Research Database (Denmark)

    Larsen, Lars Erik

    2000-01-01

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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    Human respiratory syncytial virus is an important cause of severe respiratory disease in young children, the elderly, and in immunocompromised adults. Similarly, bovine respiratory syncytial virus (BRSV) is causing severe, sometimes fatal, respiratory disease in calves. Both viruses are pneumovirus...... and 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...

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior to the o...

  4. 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. Physician

  5. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

    The protection induced by immunostimulating complexes (ISCOMs) against bovine respiratory syncytial virus (BRSV) was evaluated and compared to that of a commercial inactivated vaccine (CV) in calves with BRSV-specific maternal antibodies. Following experimental challenge, controls (n = 4) and ani......The protection induced by immunostimulating complexes (ISCOMs) against bovine respiratory syncytial virus (BRSV) was evaluated and compared to that of a commercial inactivated vaccine (CV) in calves with BRSV-specific maternal antibodies. Following experimental challenge, controls (n = 4......) and animals immunized with CV (n = 5) developed moderate to severe respiratory disease, whereas calves immunized with ISCOMS (17 = 5) remained clinically healthy. BRSV was re-isolated from the nasopharynx of all controls and from all calves immunized with CV, but from none of the calves immunized with ISCOMs....... BRSV-RNA was detected by real-time PCR from a single animal in this group. Significantly higher BRSV-specific nasal IgG, serum IgG(1) and IgG(2) titers were detected before and after challenge in animals immunized with ISCOMs versus CV. In conclusion, the ISCOMs overcame the suppressive effect...

  8. Bovine respiratory syncytial virus reinfections and decreased milk yield in dairy cattle.

    Science.gov (United States)

    van der Poel, W H; Mourits, M C; Nielen, M; Frankena, K; Van Oirschot, J T; Schukken, Y H

    1995-09-01

    The influence of Bovine Respiratory Syncytial Virus (BRSV) reinfections on the daily milk yield was studied by evaluating the milk production of 32 BRSV reinfected cows. For the estimation of milk production losses, four lactation curve models were used, including a gamma function, a second degree polynomial, and both of these models with a lag variable. Bovine respiratory syncytial virus reinfections seemed to have only a small effect on the daily milk production. Comparison of the true production with an estimated production according to the gamma function showed that the production for first lactation cows dropped 0.14 kg on average and for cows in their second or later lactation 0.56 kg on average, during 5 consecutive days in the infection period. For the second-degree polynomial model these values were respectively 0.42 kg and 0.80 kg. All calculated average production losses were relatively small and not significant (P > 0.15). The models without lag variable were more suitable than the models with the lag variable to estimate small production losses caused by BRSV reinfections. The power of this study was sufficient to detect a decrease in production of approximately 1-1.5 kg milk per cow per day. It was therefore concluded that BRSV reinfections were not associated with an important loss of milk production.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    Replication of bovine respiratory syncytial virus (BRSV) was studied in three naturally infected calves by in situ hybridization using strand-specific RNA probes. One of the calves was a 5-month-old Friesian, the other two calves were a 3-month-old and a 2-week-old Jersey. Two Jersey calves, 3 mo...

  10. Evaluation of reverse transcription-PCR protocols based on the fusion gene for diagnosis of bovine respiratory syncytial virus infections

    OpenAIRE

    Selim A.; Gaede W.

    2013-01-01

    Bovine respiratory syncytial virus (BRSV) is a pneumovirus in the family paramyxoviridae, is an important cause of acute respiratory disease in postweaning calves and feedlot cattle. The real-time reverse transcriptase PCR protocols were developed to detect BRSV infection in infected animals. The sensitivity of RT-PCR protocols based on fusion gene were evaluated using different Mastermixes such as Qiagen One Step RT-PCR (Qiagen) for conventional RT-PCR, Su...

  11. 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.

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

    Science.gov (United States)

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

  13. Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in three-week-old calves experimentally challenged with BRSV

    NARCIS (Netherlands)

    Vangeel, I.; Antonis, A.F.G.; Fluess, M.; Peters, A.R.; Harmeyer, S.S.

    2005-01-01

    Bovine respiratory syncytial virus (BRSV) is a widespread cause of lower respiratory tract disease in cattle. Calves less than four months of age are often involved in outbreaks of respiratory disease. We evaluated the efficacy of a single intranasal dose of a bivalent modified live vaccine containi

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

    Directory of Open Access Journals (Sweden)

    José Segura C.

    2013-11-01

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    Bovine respiratory syncytial virus (BRSV) is an important cause of respiratory disease among calves in the Danish cattle industry. An experimental BRSV infection model was used to study the pathogenesis of the disease in calves. Broncho alveolar lung lavage (BAL) was performed on 28 Jersey calves...... of TNF-alpha appeared on the days where severe lung lesions and clinical signs were obvious and the amounts of BRSV-antigen were at their greatest. Although Pasteurellaceae were isolated from some of the BRSV-infected calves, calves treated with antibiotics before and through the whole period...

  16. 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 ...

  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. Restriction enzyme analysis of RT-PCR amplicons as a rapid method for detection of genetic diversity among bovine respiratory syncytial virus isolates

    NARCIS (Netherlands)

    Valentova, V.; Antonis, A.F.G.; Kovarcik, K.

    2005-01-01

    Our current knowledge of antigenic variability of the bovine respiratory syncytial virus (BRSV) is quite limited and is mainly dependent on the use of monoclonal antibodies (mAb). In this study, we present not only analysis of the antigenic, but also of the genetic variability of BRSV. Using a panel

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

    Directory of Open Access Journals (Sweden)

    Thonur Leenadevi

    2012-03-01

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

  20. 牛呼吸道合胞体病毒检测方法研究进展%Progress on the Detection Methods for Bovine Respiratory Syncytial Virus

    Institute of Scientific and Technical Information of China (English)

    杨洺扬; 王炜; 李真光; 董鹏; 胡桂学; 武华; 陈立志; 程世鹏; 冷雪

    2014-01-01

    牛呼吸道合胞体病毒是引起牛呼吸道疾病的主要病原之一。进行牛呼吸道合胞体病诊断时,首先通过临床症状观察以及病理剖检变化进行初诊,然后再进行实验室诊断。其实验室检测主要依赖于病原学诊断和血清学诊断,病原学诊断方法主要包括细胞分离培养鉴定、聚合酶链反应。血清学方法包括中和试验、免疫荧光试验、酶联免疫吸附试验等。近年来聚合酶链反应!酶联免疫吸附试验等方法得到快速发展,凭借其高效、快速、灵敏性高的特点成为牛呼吸道合胞体病毒检测的常用方法。牛呼吸道合胞体病在全球范围内流行,对各国养牛业造成极大危害。论文综述了牛呼吸道合胞体病毒检测方法的研究进展,为牛呼吸道合胞体病的诊断和预防提供参考。%Bovine respiratory syncytial virus is recognized as one of the crucial causes of bovine respiratory disease,which has a marked impact on the cattle industry and the dairy industry.Bovine respiratory syncy-tial virus is preliminarily diagnosed based on the clinical symptoms and pathological anatomy changes,and then through the laboratory tests.The laboratory tests of bovine respiratory syncytial virus mainly rely on etiology diagnosis and serological diagnosis.The methods for etiology diagnosis consists of cell-culture iso-lation techniques,polymerase chain reaction.And the serological methods consists of neutralization tests, immunofluorescence method,enzyme linked immunosorbent assay.For the past few years,the experimen-tal methods,such as polymerase chain reaction and enzyme-linked immunosorbent assay were developed rapidly,and became the main methods for the diagnosis of bovine respiratory syncytial virus due to their high efficiency,rapidness and high sensitivity.The bovine respiratory syncytial disease has spread world-wide and impacted production and animal welfare in the cattle industry.The article

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

    DEFF Research Database (Denmark)

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

    2003-01-01

    Bovine respiratory syncytial virus (BRSV) has been recognised as an important pathogen in calf pneumonia for 30 years, but surprisingly few effective infection models for studies of the immune response and the pathogenesis in the natural host have been established. We present a reproducible...... temperature and 83% exhibited >5%, consolidation of the lung tissue. The disease closely resembled natural outbreaks of BRSV-related pneumonia, and detection of BRSV in nasal secretions and lung tissues confirmed the primary role of BRSV. Nine mock-inoculated control calves failed to develop respiratory...

  2. 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......The ability of a pure virus infection to induce an acute phase protein response is of interest as viral infections are normally considered to be less efficient in inducing an acute phase protein response than bacterial infections. This was studied in a bovine model for infection with bovine...

  3. A new high-speed droplet-real-time polymerase chain reaction method can detect bovine respiratory syncytial virus in less than 10 min.

    Science.gov (United States)

    Uehara, Masayuki; Matsuda, Kazuyuki; Sugano, Mitsutoshi; Honda, Takayuki

    2014-03-01

    The polymerase chain reaction (PCR) has been widely used for diagnosis of infectious diseases of domestic animals. Rapid detection of respiratory pathogens of cattle is useful for making therapeutic decisions. Therefore, we developed a new genetic-based method called droplet-real-time PCR, which can detect bovine respiratory syncytial virus (BRSV) within 10 min. Our droplet-real-time PCR markedly reduced the reaction time of reverse transcription-PCR while maintaining the same sensitivity as conventional real-time PCR, and it can be used as a rapid assay for detection of BRSV. Furthermore, our method is potentially applicable for rapid diagnosis of almost all infectious diseases, including highly pathogenic avian influenza virus.

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

    DEFF Research Database (Denmark)

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

    1999-01-01

    A reverse transcription-polymerase chain reaction (RT-PCR) assay was developed for detection of bovine respiratory syncytial virus (BRSV) in lung tissue of naturally and experimentally infected cattle. Primers were selected from the gene coding the F fusion protein, which is relatively conserved...... among BRSV isolates. The RT-PCR assay was highly specific, it yielded positive reactions only when performed on BRSV-infected cell cultures or tissues. The detection limit of the RT-PCR assay was assessed as 5 TCID50. BRSV was detected in tissues of the respiratory tract and in the tracheobroncheal....... (7%), and Pasteurella haemolytica (7%) were the most common bacterial agents found in the lungs. BRSV was identified using a conventional antigen enzyme-linked immunosorbent assay (ELISA) in 23 (17%) animals. The established BRSV-specific RT-PCR assay yielded positive results for the same 23 animals...

  5. DETECTION OF ANTIBODIES AGAINST BOVINE HERPES VIRUS 1, BOVINE VIRAL DIARRHEA VIRUS AND BOVINE RESPIRATORY SYNCYTIAL VIRUS IN EARLY AND ULTRA-EARLY WEANED BEEF CALVES

    Directory of Open Access Journals (Sweden)

    Diego Daniel Gonzalez

    2013-01-01

    Full Text Available Bovine respiratory disease is the leading cause of morbidity and mortality in weaned calves. In Argentina, two weaning practices have been implemented. In the early weaning, the calf is removed from the cow at 60-70 days of age while in ultra-early weaning the calf is weaned at 30-45 days of age. The purposes of both systems is to improve cow body condition, calf performance, conception rates and forage availability for the cow. In this study we evaluated the antibody response against BVDV and BoHV1 in early and ultra-early weaned calves that had received a conventional vaccination schedule (first dose at weaning and a booster 21 days post-weaning. Passively acquired immunity may provide protection against disease caused by these viruses. The presence of antibodies against BRSV, a virus that was not present in the vaccines used, was also evaluated as an indirect indicator of viral circulation in the herd. At the time of vaccination, calves presented a wide range of maternally-derived antibody titers. Vaccination against BoHV-1 did not evoke seroconvertion and antibody titers continued to decay throughout the experience. After vaccination, seroconversion to BVDV could be detected in calves with low antibody titers, while higher antibody titers exerted an inhibitory effect of the active humoral response.

  6. Prevalence of and risk factors for bovine respiratory syncytial virus (BRSV) infection in non-vaccinated dairy and dual-purpose cattle herds in Ecuador.

    Science.gov (United States)

    Saa, Luis Rodrigo; Perea, Anselmo; Jara, Diego Vinicio; Arenas, Antonio José; Garcia-Bocanegra, Ignacio; Borge, Carmen; Carbonero, Alfonso

    2012-10-01

    A cross-sectional study was carried out to determine the seroprevalence and risk factors associated with bovine respiratory syncytial virus (BRSV) infection in non-vaccinated dairy and dual-purpose cattle herds from Ecuador. A total of 2,367 serum samples from 346 herds were collected from June 2008 to February 2009. A questionnaire, which included variables related to cattle, health, management measures, and the environment, was filled out in each herd. Presence of antibodies against BRSV was analyzed using a commercial indirect ELISA test. A logistic regression model was used to determine risk factors associated with BRSV at herd level. The individual seroprevalence against BRSV in non-vaccinated herds in Ecuador was 80.48% [1,905/2,367; 95% confidence interval (CI) = 78.9-82.1]. The herd prevalence was 91.3% (316/346; 95% CI = 88.3-94.3), and the intra-herd prevalence ranged between 25% and 100% (mean, 90.47%). The logistic regression model showed that the existence of bordering cattle farms, the dual-purpose farms, and the altitude of the farm (more than 2,338 m above sea level) were risk factors associated with BRSV infection. This is the first study about BRSV prevalence in Ecuador. It shows the wide spread of the BRSV infection in the country. The risk factors found will help to design effective control strategies.

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

    Science.gov (United States)

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

    2014-04-01

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

  9. 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 Bir...

  10. Bovine respiratory syncytial virus: immunohistochemichal detection in mouse and bovine tissues using a Mab against human respiratory syncytial virus Vírus respiratório sincicial bovino: detecção por imunoistoquímica em tecidos de camundongos e bovinos usando AcM contra o vírus respiratório sincicial humano

    Directory of Open Access Journals (Sweden)

    R.S. Almeida

    2006-12-01

    Full Text Available An immunoistochemical (IHC test was developed to detect bovine respiratory syncytial virus (BRSV in cell cultures and tissues of experimentally infected mice and calves, using a commercial monoclonal antibody (Mab against human respiratory syncytial virus (HRSV, as a less expensive alternative, instead of producing specific monoclonal antibodies to BRSV. Clinical samples from calves suffering respiratory disease were also submitted to this test. IHC detected BRSV antigens in mouse tracheas (3, 5 and 7 days post-infection and lungs (5 and 7 days post-infection, and in one of three lungs from experimentally infected calves. Lungs samples from two naturally infected calves were tested and resulted positive for BRSV by the IHC test. These results suggest that this test may be used in the future for diagnosis as well as a useful tool to assess the distribution of BRSV infections in Brazilian herds.Desenvolveu-se um teste de imunohistoquímica (IHQ para detecção do vírus respiratório sincicial bovino (BRSV multiplicado em cultivo celular e em tecidos de camundongos e bezerros infectados experimentalmente, utilizando um anticorpo monoclonal comercial contra o vírus respiratório sincicial humano (HRSV, como uma alternativa para eliminar os custos de produção de anticorpos monoclonais específicos para o BRSV. Amostras clínicas de bezerros com sintomatologia respiratória foram analisadas. A técnica mostrou-se eficiente na detecção de antígenos do BRSV em traquéias (3, 5 e 7 dias pós-infecção e pulmões (5 e 7 dias pós-infecção dos camundongos infectados e em uma das três amostras de pulmões dos bezerros infectados experimentalmente. Amostras de pulmões de dois animais com infecção natural foram positivas para BRSV. Conclui-se que o teste de IHQ pode ser usado no diagnóstico das infecções por BRSV e na avaliação da distribuição dessas infecções nos rebanhos bovinos brasileiros.

  11. Hibridación in situ del virus respiratorio syncytial bovino en pulmón de cordero a diferentes tiempos postinfección Bovine respiratory syncytial virus in-situ hybridization from sheep lungs at different times postinfection

    Directory of Open Access Journals (Sweden)

    E. REDONDO

    2003-01-01

    Full Text Available Se estudió, mediante la técnica de hibridación in situ, la distribución del ARN viral del virus respiratorio Sincicial Bovino (VRSB en pulmón de corderos infectados en forma experimental, a diferentes tiempos postinoculación. La sonda usada para la hibridación in situ se preparó mediante transcripción reversa del ARN del VRSB, seguida de la amplificación mediante PCR de cADN. 25 corderos de raza Merino de ambos sexos y de un peso vivo de 55 (+/- 10 Kg, fueron inoculados por vía intratraqueal con 40 ml de solución salina que contenía 1.26 x 10(6 DIM50 por ml (cepa viral NMK7. Los corderos se sacrificaron los días 1, 3, 7, 11 y 15 postinoculación. Las células epiteliales bronquiales y bronquiolares resultaron positivas a los ácidos nucleicos de VRSB los días 1, 3, 7 y 11 postinoculación. A su vez, el epitelio alveolar contenía células positivas los días 1, 3, y 7 postinoculación. Se detectaron células que contenían el ARN viral en las luces bronquiales y bronquilares del día 1 al 11 postinoculación, y en el exudadado alveolar en los días 3 y 7 postinoculación. Se identificaron señales positivas de hibridación desde el día 3 al 11 postinoculación, tanto en las células intersticiales mononucleares como en el tejido linfoide asociado a los bronquios. Las señales de hibridación más intensas se detectaron a los días 3 y 7 postinoculación, lo que coincidió con las lesiones histopatológicas de mayor consideraciónWe studied the distribution of bovine respiratory syncytial virus (BRSV RNA in lungs of experimentally infected sheep by in situhybridization at different times postinfection. The probe used for in-situ hybridization was prepared by reverse transcription of BRSV RNA, followed by PCR amplification of the cDNA. Twenty five Merino sheeps of both sexes with a live weight of 55± 10 Kg, received a intratracheal inoculation of 40 ml saline solution containing 1.26 x 10(6 TCID50 BRSV (strain NMK7 per ml. Sheep

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

    Science.gov (United States)

    This study investigated viruses in bovine respiratory disease (BRD) cases in feedlots, including bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine coronaviruses (BoCV) and parainfluenza-3 virus (PI3V). Nasal swabs were collected fro...

  13. Perinatal Lamb Model of Respiratory Syncytial Virus (RSV) Infection

    Science.gov (United States)

    Derscheid, Rachel J.; Ackermann, Mark R.

    2012-01-01

    Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis in infants and children worldwide. Many animal models are used to study RSV, but most studies investigate disease in adult animals which does not address the unique physiology and immunology that makes infants more susceptible. The perinatal (preterm and term) lamb is a useful model of infant RSV disease as lambs have similar pulmonary structure including airway branching, Clara and type II cells, submucosal glands and Duox/lactoperoxidase (LPO) oxidative system, and prenatal alveologenesis. Lambs can be born preterm (90% gestation) and survive for experimentation although both preterm and term lambs are susceptible to ovine, bovine and human strains of RSV and develop clinical symptoms including fever, tachypnea, and malaise as well as mild to moderate gross and histologic lesions including bronchiolitis with epithelial injury, neutrophil infiltration and syncytial cell formation. RSV disease in preterm lambs is more severe than in term lambs; disease is progressively less in adults and age-dependent susceptibility is a feature similar to humans. Innate and adaptive immune responses by perinatal lambs closely parallel those of infants. The model is used to test therapeutic regimens, risk factors such as maternal ethanol consumption, and formalin inactivated RSV vaccines. PMID:23202468

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

    Directory of Open Access Journals (Sweden)

    Mark R. Ackermann

    2012-10-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  16. Mechanisms of respiratory syncytial virus specific T cell activation

    NARCIS (Netherlands)

    Kruijsen, D.

    2011-01-01

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

  17. Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing

    NARCIS (Netherlands)

    Simoes, Eric A. F.; Groothuis, Jessil R.; Carbonell-Estrany, Xavier; Reger, Christian H. L.; Mitchell, Ian; Fredrick, Linda M.; Kimpen, Jan L. L.

    2007-01-01

    Objective Children who experience respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) early in life have high rates of subsequent recurrent wheezing. Palivizumab, an anti-RSV monoclonal antibody, has 78% to 80% efficacy in preventing RSV hospitalization in premature infants

  18. Risk factors against bovine respiratory diseade in suckling calves from Argentina

    OpenAIRE

    García-Bocanegra, Ignacio; Arenas-Montes, Antonio José; Perea-Remujo, J.A.; Arenas-Casas, Antonio; Torralbo, A.; Borge-Rodríguez, Carmen; Carbonero-Martínez, Alfonso; Maldonado García, Alfonso

    2011-01-01

    An observacional cross-sectional study was performed to determine the risk factors associated to the main viral agents of the bovine respiratory disease: bovine herpesvirus type 1 (HVB1), bovine viral diarrhoea virus (VDVB), bovine respiratory syncytial virus (VRSB) and parainfluenza 3 virus (VPI3). Blood samples from dairy calves in the provinces of Cordova and Santa Fe (Argentina) were obtained, and an epidemiological ques-tionnaire was filled. Antibodies against studied viruses were detect...

  19. Detection of antibodies against bovine respiratory syncytial virus (BRSV in dairy cattle with different prevalences of bovine herpesvirus type 1 (BoHV-1 in São Paulo State, Brazil/ Detecção de anticorpos contra o vírus respiratório sincicial bovino (BRSV em rebanhos leiteiros com diferentes prevalências de herpesvirus bovino tipo 1 (BoHV-1 no Estado de São Paulo, Brasil

    Directory of Open Access Journals (Sweden)

    Maria da Glória Buzinaro

    Full Text Available Serum samples from three dairy farms classified as high (1, 78.6%, medium (2, 40.0% and low (3, 1.6% prevalence for bovine herpesvirus type 1 (BoHV-1 from São Paulo State, were collected to analyze the prevalence to the bovine respiratory syncytial virus (BRSV by virus neutralization test. The BRSV observed prevalences for farms 1, 2, and 3 were 45.61%, 84.42%, and 54.09%, respectively. Farm 2 showed higher prevalence to BRSV (P

  20. 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...

  1. Caesarean Section and Hospitalization for Respiratory Syncytial Virus Infection

    DEFF Research Database (Denmark)

    Kristensen, Kim; Fisker, Niels; Haerskjold, Ann

    2015-01-01

    BACKGROUND AND OBJECTIVE:: Hospitalization for respiratory syncytial virus (RSV) infection and asthma share common determinants, and meta-analyses indicate that children delivered by caesarean section (CS) are at increased risk of asthma. We aimed to investigate whether birth by CS is associated ...

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  3. Challenges and Opportunities in Developing Respiratory Syncytial Virus Therapeutics

    NARCIS (Netherlands)

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

    2015-01-01

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

  4. 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...

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  6. 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...

  7. Respiratory syncytial virus rhinosinusitis in intensive care unit patients

    Directory of Open Access Journals (Sweden)

    Alexandre Rodrigues da Silva

    2007-02-01

    Full Text Available This study reported a case of rhinosinusitis for Respiratory Syncytial Virus in Intensive Care Unit patient. The settings were Intensive Care Unit at Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil. One female HIV-infected patient with respiratory failure and circulatory shock due to splenic and renal abscesses, who developed rhinosinusitis caused by RSV and bacteria. Respiratory viruses can play a pathogenic role in airways infection allowing secondary bacterial overgrowth.

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

    Directory of Open Access Journals (Sweden)

    Soveri T

    2004-12-01

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

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

    OpenAIRE

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

    2015-01-01

    Background: Despite the research importance of rhinovirus detection in asymptomatic healthy infants, the literature remains sparse. Objective: To investigate the prevalence of respiratory syncytial virus (RSV) and rhinovirus (and its species). Methods: We conducted a cross-sectional study of 110 healthy, non-hospitalized infants without acute illness at an academic medical center from November 2013 through May 2014. We tested nasal swab specimens by using polymerase chain reaction and genetic...

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

    OpenAIRE

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

    2015-01-01

    Background Despite the research importance of rhinovirus detection in asymptomatic healthy infants, the literature remains sparse. Objective To investigate the prevalence of respiratory syncytial virus (RSV) and rhinovirus (and its species). Methods We conducted a cross-sectional study of 110 healthy, non-hospitalized infants without acute illness at an academic medical center from November 2013 through May 2014. We tested nasal swab specimens by using polymerase chain reaction and genetic se...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    OBJECTIVE: We estimated differences in the severity of respiratory syncytial virus infection attributable to genetic and environmental factors. METHODS: Record linkage data on hospitalizations attributable to respiratory syncytial virus infection were gathered on all twins (12,346 pairs) born...... in Denmark between 1994 and 2003. Latent-factor models of genetic and environmental effects were fitted to the observed data by using maximal likelihood methods. RESULTS: Identical twins resembled each other significantly more than did fraternal twins for respiratory syncytial virus hospitalization...

  12. 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

  13. 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

    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 wheezi

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

    Directory of Open Access Journals (Sweden)

    Nawal Al-Maskari

    2016-02-01

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

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

    Science.gov (United States)

    Pickles, Raymond J; DeVincenzo, John P

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  17. Preventing respiratory syncytial virus in homebound premature infants.

    Science.gov (United States)

    Austin, Jennifer

    2007-01-01

    This article explores the home health nurse's role in preventing respiratory syncytial virus (RSV) among premature infants. Thousands of children infected with RSV require hospitalization each year. Consistent contact with the infant alerts the nurse to subtle signs and symptoms of RSV infection, which may include nasal congestion, cough, low-grade fever, and malaise. By developing patient and caregiver trust, the home health nurse can implement an RSV prevention plan, leading to a decrease in hospitalization episodes of premature infants with RSV. Identification of patient risk factors contributing to RSV together with caregiver education is addressed in this article.

  18. 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 respiratory support. hMPV is present in young...

  19. 4EBP1 Is Dephosphorylated by Respiratory Syncytial Virus Infection.

    Science.gov (United States)

    Pérez-Gil, Gustavo; Landa-Cardeña, Adriana; Coutiño, Rocío; García-Román, Rebeca; Sampieri, Clara L; Mora, Silvia I; Montero, Hilda

    2015-01-01

    Respiratory syncytial virus (RSV) requires protein biosynthesis machinery to generate progeny. There is evidence that RSV might alter some translation components since stress granules are formed in their host cells. Consistent with these observations, we found that RSV induces dephosphorylation of 4EBP1 (eIF4E-binding protein), an important cellular translation factor. Our results show no correlation between the 4EBP1 dephosphorylation time and the decrease in the global rate of protein synthesis. Interestingly, treatment with rapamycin stimulates virus generation. The results suggest that RSV is a virus that still contains unknown mechanisms involved in the translation of their mRNAs through the alteration or modification of some translation factors, such as 4EBP1, possibly to favor its replicative cycle.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  2. 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

  3. Specific Dietary Oligosaccharides Increase Th1 Responses in a Mouse Respiratory Syncytial Virus Infection Model

    NARCIS (Netherlands)

    Schijf, Marcel A.; Kruijsen, Debby; Bastiaans, Jacqueline; Coenjaerts, Frank E. J.; Garssen, Johan; van Bleek, Grada M.; van't Land, Belinda

    2012-01-01

    Breast feeding reduces the risk of developing severe respiratory syncytial virus (RSV) infections in infants. In addition to maternal antibodies, other immune-modulating factors in human milk contribute to this protection. Specific dietary prebiotic oligosaccharides, similar to oligosaccharides pres

  4. Immunoprophylaxis of bovine respiratory syndrome

    Directory of Open Access Journals (Sweden)

    Rogan Dragan

    2010-01-01

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

  5. T cell responses specific for Respiratory Syncytial Virus : Aspects of antigen presentation

    NARCIS (Netherlands)

    Graaff, P.M.A. de

    2006-01-01

    Respiratory Syncytial Virus is a major cause of childhood lower respiratory tract infections. Seventy percent of all children are infected in their first year of life, and nearly all children by age three. Although the majority of patients suffer a relatively mild upper respiratory tract infection,

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Huiquan Sun

    2016-04-01

    Full Text Available Abstract Objective To explore the distribution and clinical manifestations of rhinovirus infection in wheezing children, and compare the clinical differences between rhinovirus- and respiratory syncytial virus-induced wheezing. Materials and methods This prospective cohort study was carried out in Children's Hospital of Soochow University from Dec 2012 to Nov 2014. We enrolled consecutive hospitalized children <60 months of age presented with wheezing. Clinical data including cough, fever, dyspnea, crackles were recorded by pediatricians on the first day of admission. Meanwhile, nasopharyngeal aspirates were obtained to test for respiratory viruses, by using polymerase chain reaction method for rhinovirus, human bocavirus, and human metapneumovirus, and direct immunofluorescence assay to test for respiratory syncytial virus, adenovirus, parainfluenza virus types 1–3, and influenza virus types A and B. Results Rhinovirus was a main causative agent isolated in 14.7% of the hospitalized wheezing children in Suzhou, China, being second to respiratory syncytial virus (21.0%. Different from respiratory syncytial virus infection, which peaked in winter months, rhinovirus could be detected all year round, peaked between July and September, and in November. Children with rhinovirus infection were older and presented with more often allergic sensitizations, blood eosinophilia, and leukocytosis than those of respiratory syncytial virus infection. Logistic regression analysis revealed that rhinovirus-infected children experienced earlier wheezing more often than respiratory syncytial virus children (odds ratio, 3.441; 95% confidence interval, 1.187–9.979; p = 0.023. Conclusion Rhinovirus was a main viral pathogen in wheezing children, especially in summer time. Rhinovirus-induced wheezing was different from respiratory syncytial virus, apart from seasonal epidemics; these two groups differed with regard to age, allergic sensitizations, laboratory test

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-04-01

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

  11. Inactivation of respiratory syncytial virus by detergents and disinfectants.

    Science.gov (United States)

    Krilov, L R; Harkness, S H

    1993-07-01

    The activity of a number of detergents and disinfectants against respiratory syncytial virus (RSV) was evaluated in an in vitro assay system. Equal volumes of RSV and serial 10-fold dilutions of the test agents were mixed at 4 degrees C for 5 minutes. The RSV titer in each mixture was compared with that of untreated RSV alone. In 14 experiments with input RSV titers ranging from 2.6 x 10(3) to 2 x 10(7) plaque-forming units/ml, a 10-fold dilution of 5.25% sodium hypochlorite (generic bleach) inactivated (> or = 3-log reduction in titer) the virus. With lower RSV titers inactivation was also observed at a 100-fold dilution of bleach. Fetal calf serum concentrations up to 50% as an organic load did not diminish the bleach effect. The degree of RSV inactivation was also defined for Lysol, povidone-iodine, Amphyl, Hibiclens, Osyl, ethanol and Listermint. The short contact time, the reproducible nature of the findings and the continued effectiveness with increasing organic loads all suggest that detergents and disinfectants can potentially play an important role in decreasing the spread of RSV infection.

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

    Science.gov (United States)

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

    2015-01-01

    Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described. PMID:26571015

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

    Directory of Open Access Journals (Sweden)

    Laurel J Gershwin

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

  14. Down's syndrome is a risk factor for severe lower respiratory tract infection due to respiratory syncytial virus

    NARCIS (Netherlands)

    Galleguillos, Constanza; Galleguillos, Bárbara; Larios, Guillermo; Menchaca, Gonzalo; Bont, Louis; Castro-Rodriguez, Jose A

    2016-01-01

    AIM: Previous studies have suggested that Down's syndrome is an independent risk factor for severe respiratory infection due to respiratory syncytial virus (RSV). We compared the clinical characteristics of children with and without Down's syndrome hospitalised due to RSV. METHODS: This retrospectiv

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

    NARCIS (Netherlands)

    Lukens, M.V.

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

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

    NARCIS (Netherlands)

    Kimpen, JLL; Schaad, UB

    1997-01-01

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

  18. Respiratory syncytial virus: the possible trigger of airway remodeling through matrix metalloproteinase activation?

    Institute of Scientific and Technical Information of China (English)

    WEN Fu-qiang; LIU Dai-shun

    2007-01-01

    @@ Respiratory syncytial virus (RSV) is a leading cause of epidemic respiratory tract illness in children. Severe RSV infections involving the lower respiratory tract are primarily seen in young children with naive immune systems and/or genetic predispositions. However, RSV was not recognized as a potentially serious problem in older adults until the 1970s, when outbreaks of the virus infection occurred in long-term care facilities.

  19. Prolonged sinoatrial block in an infant with respiratory syncytial viral bronchiolitis.

    Science.gov (United States)

    Haddad, Wajed; Agoudemous, Melissa; Basnet, Sangita

    2012-10-01

    Complete heart block in children admitted to the pediatric intensive care unit with respiratory syncytial viral (RSV) infections has been described. This report describes a prolonged sinoatrial block exceeding 4 s in an infant with RSV, which, to the authors' knowledge, is the longest such event described in the published literature. This block was followed by shorter episodes within the next 24 h. An extensive workup showed no other known cause of bradycardia or sinoatrial block. The infant was discharged home with 48 h Holter monitoring, which was normal. At this writing, the infant has remained asymptomatic since discharge. Respiratory syncytial viral infections may cause prolonged sinoatrial block in an otherwise healthy child.

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

    Science.gov (United States)

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

    2016-02-01

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

  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.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  3. 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...

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  5. Presentation of severe combined immunodeficiency with respiratory syncytial virus and pneumocystis co-infection.

    Science.gov (United States)

    Domínguez-Pinilla, Nerea; Allende-Martínez, Luis; Corral Sánchez, María Dolores; Arocena, Jaime de Inocencio; González-Granado, Luis Ignacio

    2015-04-01

    Severe combined immunodeficiency can cause severe, life-threatening viral, bacterial and fungal infections at an early age. We report a case of a 4-month-old boy with co-infection by respiratory syncytial virus and Pneumocystis jiroveci infection that led to recognition of severe combined immunodeficiency.

  6. The role of respiratory syncytial virus and other viral pathogens in acute otitis media.

    Science.gov (United States)

    Klein, B S; Dollete, F R; Yolken, R H

    1982-07-01

    We utilized recently developed enzyme immunoassay techniques to examine the role of selected viruses in the etiology of acute otitis media. Viral pathogens were found in middle ear fluids obtained from 13 (24%) of 53 children with acute otitis media; respiratory syncytial virus accounted for ten of the 13 viral agents identified. In addition, respiratory syncytial viral antigen was found in nasopharyngeal washings obtained from 15 of the 53 children. Seven of these children had RSV identified as the sole middle ear pathogen, whereas six children had otitis caused by Streptococcus pneumoniae as either the sole middle ear pathogen or in combination with RSV. Similarly, all three children with respiratory infections caused by influenza virus had ear infections caused by bacterial pathogens, either alone or in combination with influenza virus. These findings suggest that, in patients with viral respiratory infection, coexisting acute otitis media may be associated with the recovery of either viruses or bacteria from the middle ear exudates.

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

    OpenAIRE

    2013-01-01

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

  8. 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.

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

    Science.gov (United States)

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

    2008-01-01

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

  10. Respiratory syncytial virus infection in immunocompetent and immunocompromised murine

    Institute of Scientific and Technical Information of China (English)

    JUAN ZHOU; YU XIA CUI; XI QIANG YANG; ZHOU FU; LI PING JIANG; LI JIA WANG

    2006-01-01

    The purpose of this study is to distinguish respiratory syncytial virus (RSV) infection and immunology between immunocompetent and immunocompromised murine and to explore immune mechanism of RSV infection. At various time points after RSV infection of BALB/c mice and nude mice, pulmonary viral titers were assayed, RSV antigen was tested by direct immunofluorescent assay and immunohistochemistry. Pulmonary mRNA expressions of Toll like receptor (TLR)2 and TLR4 were assayed by RT-PCR. CD4+ cells and CD8+ cells in peripheral blood were examined by flow cytometry and plasma total IgE was assayed by ELISA. Leukocytes in bronchoalveolar lavage fluid (BALF) and pulmonary histology were identified to reflect airway inflammation. It was found that RSV titers of both mice peaked on the 3rd day post infection with a much higher level of viral titer in nude mice than in BALB/c mice and a longer viral duration in nude mice (over 9 days post infection) than in BALB/c mice (6 days post infection). RSV infection induced higher viral antigen expression in nude mice (0.267 ±0.045) than in BALB/c mice (0. 168 ± 0.031). RSV infection enhanced pulmonary TLR4 expression of BALB/c mice (51.96% ± 11.34%) and nude mice (48.96% ± 12.35%) compared with each control (34.04% ± 10.06% and 32.37% ± 9.87% respectively). CD4+ peripheral blood cells increased in RSV infected BALB/c mice (66.51% ± 2.09% ) compared with the control BALB/c mice (51.63% ± 5.90% ), and CD4+ cells and CD8+ cells were deficient in nude mice. RSV infection increased plasma total IgE in both mice, and BALB/c mice had a larger amount of IgE on the 7th day post infection (9.02 ng/ml ± 2.90 ng/ml) and on the 14th day post infection (12.76 ng/ml ± 4.15 ng/ml) than corresponding nude mice (3.72 ng/ml ± 1.06 ng/ml and 7.62 ng/ml ± 3.08 ng/ml respectively on the 7th and 14th day post infection). RSV infected nude mice had more severe airway inflammation than infected BALB/c mice. It is concluded that BALB/c mice and

  11. Vaccine safety and efficacy evaluation of a recombinant bovine respiratory syncytial virus (BRSV) with deletion of the SH gene and subunit vaccines based on recombinant human RSV proteins: N-nanorings, P and M2-1, in calves with maternal antibodies.

    Science.gov (United States)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  14. Burden of Severe Respiratory Syncytial Virus Disease Among 33–35 Weeks’ Gestational Age Infants Born During Multiple Respiratory Syncytial Virus Seasons

    Science.gov (United States)

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

    2017-01-01

    Background: 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. Methods: A pooled analysis was conducted on RSVH from 7 prospective, observational studies in the Northern Hemisphere from 2000 to 2014. Infants’ 330–356 wGA without comorbidity born during the respiratory syncytial virus season who did not receive respiratory syncytial virus immunoprophylaxis were enrolled. Data for the first confirmed RSVH during the season (+1 month) were analyzed. Incidence and hospitalization rate per 100 patient-seasons, intensive care unit admission and length of stay (LOS), oxygen support, mechanical ventilation and overall hospital LOS were assessed. Results: The pooled analysis comprised 7,820 infants; 267 experienced a confirmed RSVH at a median age of 8.4 weeks. The crude pooled RSVH incidence rate was 3.41% and the rate per 100 patient-seasons was 4.52. Median hospital LOS was 5.7 days. A total of 22.2% of infants required intensive care unit admission for a median LOS of 8.3 days. A total of 70.4% received supplemental oxygen support for a median of 4.9 days, and 12.7% required mechanical ventilation for a median of 4.8 days. Conclusions: The burden of RSVH in moderate-late, 33–35 weeks’ wGA preterm infants without comorbidities born during the viral season in Northern Hemisphere countries is substantial. Severe cases required prolonged and invasive supportive therapy. PMID:27755464

  15. Pasteurella multocida and bovine respiratory disease.

    Science.gov (United States)

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

    2007-12-01

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

  16. Application of Traditional Chinese Medical Herbs in Prevention and Treatment of Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Li Li Lin

    2016-01-01

    Full Text Available Respiratory syncytial virus (RSV is a common viral pathogen of the lower respiratory tract, which, in the absence of effective management, causes millions of cases of severe illness per year. Many of these infections develop into fatal pneumonia. In a review of English and Chinese medical literature, recent traditional Chinese medical herb- (TCMH- based progress in the area of prevention and treatment was identified, and the potential anti-RSV compounds, herbs, and formulas were explored. Traditional Chinese medical herbs have a positive effect on inhibiting viral attachment, inhibiting viral internalization, syncytial formation, alleviation of airway inflammation, and stimulation of interferon secretion and immune system; however, the anti-RSV mechanisms of TCMHs are complicated, which should be further investigated.

  17. Transcription of human respiratory syncytial virus genome RNA in vitro: requirement of cellular factor(s).

    OpenAIRE

    Barik, S

    1992-01-01

    Extracts made from human respiratory syncytial virus (RSV)-infected Hep-2 cells synthesized mRNAs encoded by all known viral genes. In contrast, RSV ribonucleoproteins purified from infected cells failed to transcribe in vitro; transcription was restored by addition of a cytoplasmic extract of uninfected Hep-2 cells, demonstrating that a cellular factor(s) has a role in RSV gene expression. Quantitation of the individual gene mRNAs transcribed in vitro revealed polarity of transcription of th...

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ma. Del Rocío Baños-Lara

    2015-01-01

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

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

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    C Lin

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

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  3. Applicability of a real-time quantitative PCR assay for diagnosis of respiratory syncytial virus infection in immunocompromised adults.

    NARCIS (Netherlands)

    Elden, L.J. van; Loon, A.M. van; Beek, A.J. van der; Hendriksen, K.A.; Hoepelman, A.I.; Kraaij, M.G.J. van; Schipper, P.; Nijhuis-Van der Sanden, M.W.G.

    2003-01-01

    Respiratory syncytial virus (RSV) accounts for the majority of respiratory virus infections, producing high mortality rates in immunocompromised patients with hematologic malignancies. The available methods for the rapid detection of RSV by antigen detection or PCR either lack sensitivity, require c

  4. Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

    Science.gov (United States)

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

    2016-01-01

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

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

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    Mohamed Abd El Fatah Mahmoud

    2013-02-01

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

  6. Epidemiological changes of respiratory syncytial virus (RSV infections in Israel.

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    Shira Hirsh

    Full Text Available RSV is the leading cause of lower respiratory-tract infections in infants and therefore demands in-depth epidemiological characterization. We investigated here the distribution of RSV types in Israel between the years 2005-2012. Clinical samples were collected from 11,018 patients hospitalized due to respiratory illnesses and were evaluated for the presence of various respiratory viruses, including RSV A and RSV B. Until 2008, each year was characterized by the presence of one dominant type of RSV. However, from 2008, both RSV A and B types were detected at significant levels, particularly among infants aged 0-2 years. Furthermore, significant changes in the RSV A and RSV B subtypes circulating in Israel since 2008 were observed. Finally, we demonstrate that, irrespectively of the changes observed in RSV epidemiology, when the pandemic H1N1pdm09 influenza virus appeared in 2009, RSV infections were delayed and were detected when infection with H1N1pdm09 had declined.

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

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    Renata Dezengrini

    2009-06-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    BACKGROUND: As respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause serious respiratory tract infections, the routes of transmission of these viruses are important to elucidate. We examined the modes of virus shedding and shedding duration of RSV and hMPV in young children...... of the five children shedding RNA in faeces had diarrhoea and children shedding RNA in sweat were either less than five weeks of age or had a chronic lung disease. RSV and hMPV RNA was shed in nasal secretions for a median of 11.5 and 5.0 days respectively (p = 0.001). More than 75% of the family members...... 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....

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

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    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.

  11. 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....

  12. Clinical characteristics and risk factors of severe respiratory syncytial virus-associated acute lower respiratory tract infections in hospitalized infants

    Institute of Scientific and Technical Information of China (English)

    Xiao-Bo Zhang; Li-Juan Liu; Li-Ling Qian; Gao-Li Jiang; Chuan-Kai Wang; Pin Jia; Peng Shi; Jin Xu; Li-Bo Wang

    2014-01-01

    Background: To investigate the clinical characteristics and analyze risk factors for severe respiratory syncytial virus (RSV) infection in hospitalized infants with acute lower respiratory tract infections (ALRIs). Methods: A retrospective review of the medical records of infants with RSV-associated ALRIs between March 1st, 2011 and February 29th, 2012 was conducted. Subjects were followed up over the phone or by outpatient visit six and twelve months after discharge. Results: Among 913 RSV-associated ALRIs infants, 288 (31.5%) had severe infections, which accounted for 4.2% of hospitalized children. The hospital RSV mortality rate was 1.0%. The proportions of cases with tachypnea, apnea, cyanosis, and fine rales were significantly higher in the severe ALRIs group (all P Conclusions: Younger age, low birth weight and underlying disease are associated with severe RSVassociated ALRIs. Furthermore, severe RSV infections may be associated with a higher frequency of subsequent bronchitis, pneumonia and re-hospitalization in the following year.

  13. Cytokines and chemokines in respiratory secretion and severity of disease in infants with respiratory syncytial virus (RSV) infection

    DEFF Research Database (Denmark)

    Hornsleth, Allan; Loland, Lotte; Larsen, Lars B.

    2001-01-01

    Background: little is known about inflammatory mediators (IM); like cytokines, chemokines and receptors; in respiratory secretion as possible indicators of the severity of respiratory syncytial virus (RSV) disease. Nor have systematic studies been published on the ratios between IM...... as such indicators. Objective: to define the role of IM ratios as possible indicators of the severity of RSV disease. Study design: about 46 infants aged 0-9 months with acute RSV infections were studied. Prematurity (PM) and/or underlying disease (UD) were present in 11 of them. The concentrations of seven...... from 0 to 3 according to the severity of disease. Results: when 25 patients with severe disease (CS 2-3) and 21 patients with mild disease (CS 0-1) were compared with respect to different IM ratios, three ratios were related to severity of disease: IL-1/RANTES, IL-8/RANTES and TNF-R1/RANTES. When 12...

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

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    Bosco A Paes

    2011-01-01

    Full Text Available Respiratory syncytial virus (RSV is a common infection in infancy, with nearly all children affected by two years of age. Approximately 0.5% to 2.0% of all children are hospitalized with lower respiratory tract disease, of which 50% to 90% have bronchiolitis and 5% to 40% have pneumonia. Morbidity and mortality are highest in children with nosocomial infection and in those with underlying medical illnesses such as cardiac and chronic lung disease. Aboriginal children residing in remote northern regions are specifically considered to be at high risk for hospitalization due to RSV infection. Thorough hand washing and health education are the principal strategies in primary prevention. In the absence of a vaccine, palivizumab prophylaxis is currently the best intervention to reduce the burden of illness and RSV-related hospitalization in high-risk children. Health care professionals should provide palivizumab prophylaxis cost effectively in accordance with recommendations issued by pediatric societies and national advisory bodies.

  15. Spontaneous Pneumothorax With Subcutaneous Emphysema: A Rare Complication of Respiratory Syncytial Virus Infection.

    Science.gov (United States)

    Silva, Carmen; Almeida, Ana Filipe; Ferraz, Catarina; Nunes, Teresa; Guedes Vaz, Luisa

    2016-03-01

    Viral bronchiolitis is the most common lower respiratory tract infection in infants and children under the age of 2. Respiratory syncytial virus (RSV) is the infecting agent in more than 50% of the cases. Usually the clinical course is uneventful and complications are uncommon. Secondary air leaks are a recognized rare complication of bronchiolitis, although the real incidence remains unknown. We report a case of a 21-month-old female that developed a spontaneous pneumothorax (PNO) with subcutaneous emphysema (SE) late in the course of RSV acute bronchiolitis. Additional investigation ruled out any underlying disease predisposing to spontaneous PNO. Physicians, especially those who work with small children, must be aware of this uncommon complication of bronchiolitis that may appear late in the course of the disease despite an initial clinical improvement.

  16. Respiratory syncytial virus infection in infants and correlation with meteorological factors and air pollutants

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    Vandini Silvia

    2013-01-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV is the most important cause of severe respiratory infections in infants with seasonal epidemics. Environmental factors (temperature, humidity, air pollution could influence RSV epidemics through their effects on virus activity and diffusion. Methods We conducted a retrospective study on a paediatric population who referred to our Paediatric Emergency Unit in order to analyze the correlation between weekly incidence of RSV positive cases during winter season in Bologna and meteorological factors and air pollutants concentration. Results We observed a significant correlation between the incidence of RSV infections and the mean minimum temperature registered during the same week and the previous weeks. The weekly number of RSV positive cases was also correlated to the mean PM10 concentration of the week before. Conclusions RSV epidemic trend in Bologna (Italy is related to the mean minimum temperature, and the mean PM10 concentration.

  17. Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

    Science.gov (United States)

    Rossey, Iebe; Gilman, Morgan S. A.; Kabeche, Stephanie C.; Sedeyn, Koen; Wrapp, Daniel; Kanekiyo, Masaru; Chen, Man; Mas, Vicente; Spitaels, Jan; Melero, José A.; Graham, Barney S.; Schepens, Bert; McLellan, Jason S.; Saelens, Xavier

    2017-01-01

    Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV. PMID:28194013

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    -confirmed RSV hospital contacts at age 14-23 months in all children born in Denmark 1997-2002 who had already received the vaccine against diphtheria, tetanus, pertussis (acellular), polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) at the recommended ages of 3, 5, and 12 months. RESULTS: The study......BACKGROUND: The live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. The live measles-mumps-rubella vaccine has also been associated with lower rate of admissions with any type of infection in Danish children; the association...... was strongest for admissions with lower respiratory infections. OBJECTIVE: To examine whether measles, mumps, and rubella (MMR) vaccination was associated with reduced rate of hospital contact related to respiratory syncytial virus (RSV) in a high-income country. METHODS: Nationwide cohort study of laboratory...

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

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    Adriana Gut Lopes Riccetto

    2009-02-01

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

  20. Circulating strains of human respiratory syncytial virus in central and south America.

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    Merly Sovero

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of viral lower respiratory tract infections among infants and young children. HRSV strains vary genetically and antigenically and have been classified into two broad subgroups, A and B (HRSV-A and HRSV-B, respectively. To date, little is known about the circulating strains of HRSV in Latin America. We have evaluated the genetic diversity of 96 HRSV strains by sequencing a variable region of the G protein gene of isolates collected from 2007 to 2009 in Central and South America. Our results show the presence of the two antigenic subgroups of HRSV during this period with the majority belonging to the genotype HRSV-A2.

  1. Protection against respiratory disease in calves induced by vaccines containing respiratory syncytial virus, parainfluenza type 3 virus, Mycoplasma bovis and M dispar.

    Science.gov (United States)

    Howard, C J; Stott, E J; Thomas, L H; Gourlay, R N; Taylor, G

    1987-10-17

    A field trial to assess the ability of two vaccines to protect calves against respiratory disease was carried out on a large beef rearing unit in southern England over the two winters of 1983 to 1984 and 1984 to 1985. A quadrivalent vaccine containing the killed antigens of respiratory syncytial virus, parainfluenza virus type 3, Mycoplasma bovis and M dispar or a vaccine containing only the respiratory syncytial virus component were inoculated into 246 and 245 calves, respectively; 245 calves remained as unvaccinated controls. The calves were reared in seven batches and outbreaks of disease occurred in five; significant protection was achieved in the four batches in which disease was associated with respiratory syncytial virus and M bovis infection, together or independently. The death rate from pneumonia was 9 per cent in the control group, 2 per cent in the calves inoculated with the quadrivalent vaccine (P less than 0.001), a protection rate of 77 per cent, and 3 per cent in the calves inoculated with the respiratory syncytial virus vaccine (P less than 0.01), a protection rate of 68 per cent. The proportion of calves receiving treatment for respiratory disease was 38 per cent in the control group, 25 per cent in the calves inoculated with the quadrivalent vaccine (P less than 0.001) and 27 per cent in the calves inoculated with the respiratory syncytial virus vaccine (P less than 0.01). The results show that protection against respiratory disease can be achieved by parenteral vaccination of calves with the appropriate inactivated microorganisms.

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

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    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.

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

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    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.

  4. Exploring the association between severe respiratory syncytial virus infection and asthma: a registry-based twin study

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis; van der Sluis, Sophie; Stensballe, Lone G;

    2009-01-01

    RATIONALE: Severe respiratory syncytial virus (RSV) infection is associated with asthma but the nature of this association is imperfectly understood. OBJECTIVES: To examine the nature of the association between severe RSV infection and asthma in a population-based sample of twins. METHODS: Data...

  5. Intranasal Administration of Antibody-Bound Respiratory Syncytial Virus Particles Efficiently Primes Virus-Specific Immune Responses in Mice

    NARCIS (Netherlands)

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

    2013-01-01

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

  6. Diagnostic virology practices for respiratory syncytial virus and influenza virus among children in the hospital setting: a national survey.

    Science.gov (United States)

    Jafri, Hasan S; Ramilo, Octavio; Makari, Doris; Charsha-May, Deborah; Romero, José R

    2007-10-01

    A survey was sent to the emergency room and laboratory directors of 400 randomly selected US hospitals to assess the diagnostic testing practices for respiratory syncytial virus and influenza virus in children. The results demonstrate that the majority of hospitals routinely perform viral testing for both viruses and use virology testing practices appropriate for the reasons reported for testing.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  8. 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 infe

  9. Crawling with Virus: Translational Insights from a Neonatal Mouse Model on the Pathogenesis of Respiratory Syncytial Virus in Infants.

    Science.gov (United States)

    You, Dahui; Saravia, Jordy; Siefker, David; Shrestha, Bishwas; Cormier, Stephania A

    2015-10-07

    The infant immune response to respiratory syncytial virus (RSV) remains incompletely understood. Here we review the use of a neonatal mouse model of RSV infection to mimic severe infection in human infants. We describe numerous age-specific responses, organized by cell type, observed in RSV-infected neonatal mice and draw comparisons (when possible) to human infants.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    1997-01-01

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

  12. Immunogenicity and Protective Capacity of a Virosomal Respiratory Syncytial Virus Vaccine Adjuvanted with Monophosphoryl Lipid A in Mice

    NARCIS (Netherlands)

    Kamphuis, Tobias; Meijerhof, Tjarko; Stegmann, Toon; Lederhofer, Julia; Wilschut, Jan; de Haan, Aalzen

    2012-01-01

    Respiratory Syncytial Virus (RSV) is a major cause of viral brochiolitis in infants and young children and is also a significant problem in elderly and immuno-compromised adults. To date there is no efficacious and safe RSV vaccine, partially because of the outcome of a clinical trial in the 1960s w

  13. Timing of infection and prior immunization with respiratory syncytial virus (RSV) in RSV-enhanced allergic inflammation

    NARCIS (Netherlands)

    M. Barends (Marion); C.G. de Rond; J.A.M.A. Dormans (Jan); A.D.M.E. Osterhaus (Albert); H.J. Neijens (Herman); T.G. Kimman

    2004-01-01

    textabstractRespiratory syncytial virus (RSV) infection has been shown to be a risk factor for the development of allergy in humans and mice. The allergy-enhancing properties of RSV may be dependent on atopic background and an individual's history of RSV infection. We examined the influence of the t

  14. An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection

    NARCIS (Netherlands)

    Vissers, M.; Habets, M.N.; Ahout, I.M.L.; Jans, J.; Jonge, M.I. de; Diavatopoulos, D.A.; Ferwerda, G.

    2013-01-01

    Human respiratory syncytial virus (HRSV) infections present a broad spectrum of disease severity, ranging from mild infections to life-threatening bronchiolitis. An important part of the pathogenesis of severe disease is an enhanced immune response leading to immunopathology. Here, we describe a pro

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

    Science.gov (United States)

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

  16. 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.

  17. Development of a high-throughput replicon assay for the identification of respiratory syncytial virus inhibitors.

    Science.gov (United States)

    Tiong-Yip, Choi-Lai; Plant, Helen; Sharpe, Paul; Fan, Jun; Rich, Kirsty; Gorseth, Elise; Yu, Qin

    2014-01-01

    Respiratory syncytial virus (RSV) drug discovery has been hindered by the lack of good chemistry starting points and would benefit from robust and convenient assays for high-throughput screening (HTS). In this paper, we present the development and optimization of a 384-well RSV replicon assay that enabled HTS for RSV replication inhibitors with a low bio-containment requirement. The established replicon assay was successfully implemented for high-throughput screening. A validation screen was performed which demonstrated high assay performance and reproducibility. Assay quality was further confirmed via demonstration of appropriate pharmacology for different classes of RSV replication tool inhibitors. RSV replicon and cytotoxicity assays were further developed into a multiplexed format that measured both inhibition of viral replication and cytotoxicity from the same well. This provided a time and cost efficient approach to support lead optimization. In summary, we have developed a robust RSV replicon assay to help expedite the discovery of novel RSV therapeutics.

  18. 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......+ T-cell responses were not induced. Thus, in addition to specific CD8+ T cell-mediated immunopathology, gene-gun DNA vaccination causes non-specific enhancement of RSV disease without affecting virus clearance....

  19. Potential therapeutic implications of new insights into respiratory syncytial virus disease

    Directory of Open Access Journals (Sweden)

    Openshaw Peter JM

    2002-06-01

    Full Text Available Abstract Viral bronchiolitis is the most common cause of hospitalization in infants under 6 months of age, and 70% of all cases of bronchiolitis are caused by respiratory syncytial virus (RSV. Early RSV infection is associated with respiratory problems such as asthma and wheezing later in life. RSV infection is usually spread by contaminated secretions and infects the upper then lower respiratory tracts. Infected cells release proinflammatory cytokines and chemokines, including IL-1, tumor necrosis factor-α, IL-6, and IL-8. These activate other cells and recruit inflammatory cells, including macrophages, neutrophils, eosinophils, and T lymphocytes, into the airway wall and surrounding tissues. The pattern of cytokine production by T lymphocytes can be biased toward 'T-helper-1' or 'T-helper-2' cytokines, depending on the local immunologic environment, infection history, and host genetics. T-helper-1 responses are generally efficient in antiviral defense, but young infants have an inherent bias toward T-helper-2 responses. The ideal intervention for RSV infection would be preventive, but the options are currently limited. Vaccines based on protein subunits, live attenuated strains of RSV, DNA vaccines, and synthetic peptides are being developed; passive antibody therapy is at present impractical in otherwise healthy children. Effective vaccines for use in neonates continue to be elusive but simply delaying infection beyond the first 6 months of life might reduce the delayed morbidity associated with infantile disease.

  20. Altered cardiac rhythm in infants with bronchiolitis and respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Galeone Carlotta

    2010-10-01

    Full Text Available Abstract Background Although the most frequent extra-pulmonary manifestations of respiratory syncytial virus (RSV infection involve the cardiovascular system, no data regarding heart function in infants with bronchiolitis associated with RSV infection have yet been systematically collected. The aim of this study was to verify the real frequency of heart involvement in patients with bronchiolitis associated with RSV infection, and whether infants with mild or moderate disease also risk heart malfunction. Methods A total of 69 otherwise healthy infants aged 1-12 months with bronchiolitis hospitalised in standard wards were enrolled. Pernasal flocked swabs were performed to collect specimens for the detection of RSV by real-time polymerase chain reaction, and a blood sample was drawn to assess troponin I concentrations. On the day of admission, all of the infants underwent 24-hour Holter ECG monitoring and a complete heart evaluation with echocardiography. Patients were re-evaluated by investigators blinded to the etiological and cardiac findings four weeks after enrolment. Results Regardless of their clinical presentation, sinoatrial blocks were identified in 26/34 RSV-positive patients (76.5% and 1/35 RSV-negative patients (2.9% (p Conclusions RSV seems associated with sinoatrial blocks and transient rhythm alterations even when the related respiratory problems are mild or moderate. Further studies are needed to clarify the mechanisms of these rhythm problems and whether they remain asymptomatic and transient even in presence of severe respiratory involvement or chronic underlying disease.

  1. Respiratory Syncytial Virus and Other Respiratory Viral Infections in Older Adults With Moderate to Severe Influenza-like Illness

    Science.gov (United States)

    Falsey, Ann R.; McElhaney, Janet E.; Beran, Jiri; van Essen, Gerrit A.; Duval, Xavier; Esen, Meral; Galtier, Florence; Gervais, Pierre; Hwang, Shinn-Jang; Kremsner, Peter; Launay, Odile; Leroux-Roels, Geert; McNeil, Shelly A.; Nowakowski, Andrzej; Richardus, Jan Hendrik; Ruiz-Palacios, Guillermo; St Rose, Suzanne; Devaster, Jeanne-Marie; Oostvogels, Lidia; Durviaux, Serge; Taylor, Sylvia

    2014-01-01

    Background. Few studies have prospectively assessed viral etiologies of acute respiratory infections in community-based elderly individuals. We assessed viral respiratory pathogens in individuals ≥65 years with influenza-like illness (ILI). Methods. Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal/throat swabs from 556 episodes of moderate-to-severe ILI, defined as ILI with pneumonia, hospitalization, or maximum daily influenza symptom severity score (ISS) >2. Cases were selected from a randomized trial of an adjuvanted vs nonadjuvanted influenza vaccine conducted in elderly adults from 15 countries. Results. Respiratory syncytial virus (RSV) was detected in 7.4% (41/556) moderate-to-severe ILI episodes in elderly adults. Most (39/41) were single infections. There was a significant association between country and RSV detection (P = .004). RSV prevalence was 7.1% (2/28) in ILI with pneumonia, 12.5% (8/64) in ILI with hospitalization, and 6.7% (32/480) in ILI with maximum ISS > 2. Any virus was detected in 320/556 (57.6%) ILI episodes: influenza A (104/556, 18.7%), rhinovirus/enterovirus (82/556, 14.7%), coronavirus and human metapneumovirus (each 32/556, 5.6%). Conclusions. This first global study providing data on RSV disease in ≥65 year-olds confirms that RSV is an important respiratory pathogen in the elderly. Preventative measures such as vaccination could decrease severe respiratory illnesses and complications in the elderly. PMID:24482398

  2. Impact of severe disease caused by respiratory syncytial virus in children living in developed countries.

    Science.gov (United States)

    Simoes, Eric A; Carbonell-Estrany, Xavier

    2003-02-01

    Among industrialized nations, the rate of rehospitalization in the United States for respiratory syncytial virus (RSV) is approximately 30 per 1000, exceptions being noted for American Indians and Alaskan natives, two ethnic groups who tend toward higher rates of RSV hospitalization. In distinction Japan reports an admission rate of 60 per 1000 for RSV disease. Yet Japan ranks considerably lower than many of its western counterparts in premature births. Whether an RSV subtype, a new viral genotype or some other unifying characteristic exists that might explain the severity of adenovirus, parainfluenza and RSV infections in this region of Asia remains to be determined. Outcomes trials in the United States, Canada, United Kingdom, Denmark and Japan all identified crowding and exposure to tobacco smoke as significant and independent risk factors for disease severity of RSV. The epidemiology of RSV is largely consistent throughout Europe, with peak outbreaks occurring in December and January. In Europe RSV accounts for 42 to 45% of hospital admissions for lower respiratory tract infections in children younger than 2 years of age, and inpatient populations tend to be younger and to experience greater disease severity. For RSV bronchiolitis lengths of stay in European hospitals range from a low of 4 days to a high of 10 days. The Infección Respiratoria Infantil por Virus Respiratorio Sincitial Study Group in Spain conducted 2 prospective observational studies in 14 and 26 neonatal units, respectively, on nonprophylaxed neonates to determine hospitalization rates for respiratory syncytial viral illness during 2 consecutive RSV seasons. Throughout each respiratory season the study group followed premature infants of < or =32 weeks gestational age at birth, representing an annual birth cohort of approximately 100 000 infants. A total of 584 infants who were < or =32 weeks gestational age in the first season and 999 in the second season were followed at monthly intervals

  3. [Preliminary analysis on respiratory syncytial virus identified in children with acute respiratory infections in Tibet Autonomous Region, China].

    Science.gov (United States)

    Deng, Jie; Zhu, Ru-Nan; Qian, Yuan; Sun, Yu; Zhao, Lin-Qing; Wang, Fang; Wu, Hong; Shan, Min-Na; Deji, Mei-Duo

    2012-03-01

    To understand the role of respiratory syncytial virus (RSV) in children with acute respiratory infections (ARI) in Tibet Autonomous Region and the contribution of two major groups of RSV, nasopharyngeal aspirates (NPA) were collected from hospitalized children with ARI in Department of Pediatrics, Tibet People's Hospital in Lasa, Tibet from April to July in 2011 and tested for seven common respiratory viruses and human metapneumovirus (hMPV) by direct immunofluorescence assay (DFA). Total RNAs were extracted from RSV positive samples by DFA and reverse transcripted to cDNA. Nested-PCR was employed to determine the genogroups of RSV, which were confirmed by real time-PCR and sequence analysis for G protein encoding gene. The Characteristics and variations of G genes from RSV in this project were identified by sequence comparison with those G genes in GenBank. Out of 167 samples, 65 were positive for respiratory viruses with a total positive rate of 38.9%, including 45 (69.2%, 45/65)positive samples for RSV. Among 42 samples that were positive for RSV and genotyped, 40 were identified as group A and 2 as group B. Sequence analysis of full-length G genes for 7 RSV of group A indicated that all of these belonged to subgroup GA2. The nucleotide identities between RSVs from Tibet and prototype A2 strain were 90.7%-91.8%, with 86.5%-87.2% identities of amino acid. The mutations of amino acids were mainly located in both ends of a highly conserved region in the ectodomain of the G proteins. The data indicated that RSV was the most important viral etiologic agent of ARI in spring of 2011 in Tibet and group A of RSV was predominant during the study period. High divergence existed in the ectodomain of G proteins of RSVs from Tibet.

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

    Science.gov (United States)

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

    2017-01-01

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

  5. Interferon gamma Profile in Egyptian Infants with Respiratory Syncytial Virus bronchiolitis

    Directory of Open Access Journals (Sweden)

    Maha E. Omran1, Mohamed AE. Fahmy2, Manal M. Zaher3

    2008-03-01

    Full Text Available Viral bronchiolitis is one of the leading causes for hospitalization of infants in the world and causes an estimated one million deaths per year worldwide. Respiratory syncytial virus (RSV is associated with the majority of cases. During the last few years it has become increasingly clear that T cells contribute to the abnormal regulation of the immune response in viral diseases since these cells are potent producers of a large variety of cytokines. It was reported that cord blood interferon gamma (IFN- responses were inversely related to the frequency of viral respiratory infections. To ascertain whether RSV infection promotes a different IFN- profile to that induced by other respiratory infections, thirty-two infants with severe bronchiolitis were enrolled in this study. RSV-IgM was detected by immunofluorescent technique in 23/32 patients. Serum IFN- levels in RSV+ infants were significantly lower than RSV- (p < 0.001. In vitro stimulation of peripheral blood cells followed by flow cytometery combined with intracellular cytokine staining revealed that both CD4+ and CD8+ cells contribute in IFN- production. The percentage of CD4+ cells producing IFN- in RSV+ was significantly lower (P < 0.05 than those in RSV-, while the difference in % of CD8+ between RSV+ and RSV- was non significant. Our conclusions are that RSV infection is associated with severe decreased IFN- responses. Both CD4+ and CD8+ cells contribute in IFN- production during RSV bronchiolitis. RSV infection promotes a different IFN- profile from that induced by other respiratory infections.

  6. Comparison of severe pneumonia caused by Human metapneumovirus and respiratory syncytial virus in hospitalized children

    Directory of Open Access Journals (Sweden)

    Yuqing Wang

    2014-01-01

    Full Text Available Objectives: The objective of this study is to compare the incidence and clinical characteristics of severe pneumonia caused by Human metapneumovirus (hMPV to respiratory syncytial virus (RSV infection in children. Patients and Methods: A total of 151 children hospitalized with severe pneumonia, were tested for hMPV using reverse-transcription polymerase chain reaction. At the same time, samples were tested for RSV and other common respiratory viruses. Medical records, including clinical, laboratory data, and chest radiography findings, were reviewed for all children. Results: Of the 151 samples, 88 (58.3% were positive for respiratory viruses. Of the 88 positive, there were 6 (4.0% with hMPV, 66 (43.7% with RSV, 13 (8.6% with influenza A, 2 (1.3% with parainfluenza virus III, 1 (0.7% with parainfluenza virus I, 1 (0.7% with adenovirus and 1 (0.7% with influenza B. hMPV-infected patients were significantly older than RSV-infected patients (P < 0.001. Children with hMPV pneumonia had fever more frequently (P = 0.03. Two hMPV-positive patients (33.3% required admission to an intensive care unit, and two patients (33.3% required mechanical ventilation. The duration of illness was 18.33 ± 7.09 days. These characteristics of hMPV infections were similar to patients with RSV infections. Conclusion: Human metapneumovirus is an infrequent viral pathogen causing severe pneumonia in children. Children with hMPV were older than those with RSV. The disease caused by hMPV was similar in presentation and severity to RSV, with a minority of children requiring additional respiratory support.

  7. Lamb Model of Respiratory Syncytial Virus–Associated Lung Disease: Insights to Pathogenesis and Novel Treatments

    Science.gov (United States)

    Ackermann, Mark R.

    2014-01-01

    Preterm birth is a risk factor for respiratory syncytial virus (RSV) bronchiolitis and hospitalization. The pathogenesis underlying this is not fully understood, and in vivo studies are needed to better clarify essential cellular features and molecular mechanisms. Such studies include analysis of lung tissue from affected human infants and various animal models. The preterm and newborn lamb lung has developmental, structural, cellular, physiologic, and immunologic features similar to that of human infants. Also, the lamb lung is susceptible to various strains of RSV that infect infants and cause similar bronchiolar lesions. Studies in lambs suggest that viral replication in airways (especially bronchioles) is extensive by 4 days after infection, along with bronchiolitis characterized by degeneration and necrosis of epithelial cells, syncytial cell formation, neutrophil infiltration, epithelial cell hypertrophy and hyperplasia, and innate and adaptive immune responses. RSV bronchiolitis greatly affects airflow and gaseous exchange. RSV disease severity is increased in preterm lambs compared with full-term lambs; similar to human infants. The lamb is conducive to experimental assessment of novel, mechanistic therapeutic interventions such as delivery of vascular endothelial growth factor and enhancement of airway epithelial oxidative responses, Club (Clara) cell protein 10, and synthesized compounds such as nanobodies. In contrast, exposure of the fetal ovine lung in vivo to ethanol, a risk factor for preterm birth, reduces pulmonary alveolar development and surfactant protein A expression. Because the formalin-inactivated RSV vaccination enhances some inflammatory responses to RSV infection in lambs, this model has the potential to assess mechanisms of formalin-inactivated RSV enhanced disease as well as newly developed vaccines. PMID:24936027

  8. Immunological Features of Respiratory Syncytial Virus-Caused Pneumonia—Implications for Vaccine Design

    Science.gov (United States)

    Rey-Jurado, Emma; Kalergis, Alexis M.

    2017-01-01

    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. PMID:28273842

  9. Pattern recognition receptors for respiratory syncytial virus infection and design of vaccines.

    Science.gov (United States)

    Zeng, Ruihong; Cui, Yuxiu; Hai, Yan; Liu, Ying

    2012-08-01

    Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants and young children. Host immune response has been implicated in both the protection and immunopathological mechanisms. Pattern recognition receptors (PRRs) expressed on innate immune cells during RSV infection recognize the RSV-associated molecular patterns and activate innate immune cells as well as mediate airway inflammation, protective immune response, and pulmonary immunopathology. The resident and recruited innate immune cells play important roles in the protection and pathogenesis of an RSV disease by expressing these PRRs. Agonist-binding PRRs are the basis of many adjuvants that are essential for most vaccines. In the present review, we highlight recent advances in the innate immune recognition of and responses to RSV through PRRs, including toll-like receptors (TLRs), retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). We also describe the role of PRRs in the design of RSV vaccines.

  10. Sirtuin 1 Regulates Dendritic Cell Activation and Autophagy during Respiratory Syncytial Virus-Induced Immune Responses.

    Science.gov (United States)

    Owczarczyk, Anna B; Schaller, Matthew A; Reed, Michelle; Rasky, Andrew J; Lombard, David B; Lukacs, Nicholas W

    2015-08-15

    Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in children worldwide. Sirtuin 1 (SIRT1), an NAD(+)-dependent deacetylase, has been associated with the induction of autophagy and the regulation of inflammatory mediators. We found that Sirt1 was upregulated in mouse lung after RSV infection. Infected animals that received EX-527, a selective SIRT1 inhibitor, displayed exacerbated lung pathology, with increased mucus production, elevated viral load, and enhanced Th2 cytokine production. Gene expression analysis of isolated cell populations revealed that Sirt1 was most highly upregulated in RSV-treated dendritic cells (DCs). Upon RSV infection, EX-527-treated DCs, Sirt1 small interfering RNA-treated DCs, or DCs from conditional knockout (Sirt1(f/f)-CD11c-Cre(+)) mice showed downregulated inflammatory cytokine gene expression and attenuated autophagy. Finally, RSV infection of Sirt1(f/f)-CD11c-Cre(+) mice resulted in altered lung and lymph node cytokine responses, leading to exacerbated pathology. These data indicate that SIRT1 promotes DC activation associated with autophagy-mediated processes during RSV infection, thereby directing efficient antiviral immune responses.

  11. Biophysical characterization of G protein ectodomain of group B human respiratory syncytial virus from E. coli.

    Science.gov (United States)

    Khan, Wajihul Hasan; Srungaram, V L N Raghuram; Islam, Asimul; Beg, Ilyas; Haider, Md Shakir H; Ahmad, Faizan; Broor, Shobha; Parveen, Shama

    2016-07-03

    Human respiratory syncytial virus (hRSV) is an important pathogen of acute respiratory tract infection. The G protein of hRSV is a transmembrane glycoprotein that is a neutralizing antigen and is thus a vaccine candidate. In this study, synthetic codon optimized ectodomain G protein [G(ΔTM)] of BA genotype of group B hRSV was cloned, expressed, and characterized using biophysical techniques. The molar absorption coefficient and mean residue ellipticity at 222 nm ([θ]222) of G (ΔTM) was found to be 7950 M(-1) cm(-1) and -19701.7 deg cm(2) dmol(-1) respectively. It was concluded that G(ΔTM) mainly consist of α-helix (74.9%) with some amount of β-sheet (4%). The protein was stable up to 85°C without any transition curve. However, heat-induced denaturation of G(ΔTM) resulted in total loss of β-sheet whereas not much change was observed in the α-helix part of the secondary structure. It was concluded that G(ΔTM) is an α-helical protein and it is highly stable at high temperature, but could be easily denatured using high concentrations of GdmCl/urea or acidic condition. This is the first investigation of cloning, expression, and characterization of G(ΔTM) of BA viruses from India. Structural characterization of G protein will assist in drug designing and vaccine development for hRSV.

  12. Inhibition of respiratory syncytial virus replication and virus-induced p38 kinase activity by berberine.

    Science.gov (United States)

    Shin, Han-Bo; Choi, Myung-Soo; Yi, Chae-Min; Lee, Jun; Kim, Nam-Jung; Inn, Kyung-Soo

    2015-07-01

    Respiratory syncytial virus (RSV) causes severe lower respiratory tract infection and poses a major public health threat worldwide. No effective vaccines or therapeutics are currently available; berberine, an isoquinoline alkaloid from various medicinal plants, has been shown to exert antiviral and several other biological effects. Recent studies have shown that p38 mitogen-activated protein kinase (MAPK) activity is implicated in infection by and replication of viruses such as RSV and the influenza virus. Because berberine has previously been implicated in modulating the activity of p38 MAPK, its effects on RSV infection and RSV-mediated p38 MAPK activation were examined. Replication of RSV in epithelial cells was significantly reduced by treatment with berberine. Berberine treatment caused decrease in viral protein and mRNA syntheses. Similar to previously reported findings, RSV infection caused phosphorylation of p38 MAPK at a very early time point of infection, and phosphorylation was dramatically reduced by berberine treatment. In addition, production of interleukin-6 mRNA upon RSV infection was significantly suppressed by treatment with berberine, suggesting the anti-inflammatory role of berberine during RSV infection. Taken together, we showed that berberine, a natural compound already proven to be safe for human consumption, suppresses the replication of RSV. In addition, the current study suggests that inhibition of RSV-mediated early p38 MAPK activation, which has been implicated as an early step in viral infection, as a potential molecular mechanism.

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

    Science.gov (United States)

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

    2013-08-01

    Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection. Infection is critically dependent on the RSV fusion (F) protein, which mediates fusion between the viral envelope and airway epithelial cells. The F protein is also expressed on infected cells and is responsible for fusion of infected cells with adjacent cells, resulting in the formation of multinucleate syncytia. The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor that is constitutively highly expressed by type I alveolar epithelial cells. Here, we report that RAGE protected HEK cells from RSV-induced cell death and reduced viral titres in vitro. RAGE appeared to interact directly with the F protein, but, rather than inhibiting RSV entry into host cells, virus replication and budding, membrane-expressed RAGE or soluble RAGE blocked F-protein-mediated syncytium formation and sloughing. These data indicate that RAGE may contribute to protecting the lower airways from RSV by inhibiting the formation of syncytia, viral spread, epithelial damage and airway obstruction.

  14. 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.

  15. Retrospective Parameter Estimation and Forecast of Respiratory Syncytial Virus in the United States

    Science.gov (United States)

    Shaman, Jeffrey

    2016-01-01

    Recent studies have shown that systems combining mathematical modeling and Bayesian inference methods can be used to generate real-time forecasts of future infectious disease incidence. Here we develop such a system to study and forecast respiratory syncytial virus (RSV). RSV is the most common cause of acute lower respiratory infection and bronchiolitis. Advanced warning of the epidemic timing and volume of RSV patient surges has the potential to reduce well-documented delays of treatment in emergency departments. We use a susceptible-infectious-recovered (SIR) model in conjunction with an ensemble adjustment Kalman filter (EAKF) and ten years of regional U.S. specimen data provided by the Centers for Disease Control and Prevention. The data and EAKF are used to optimize the SIR model and i) estimate critical epidemiological parameters over the course of each outbreak and ii) generate retrospective forecasts. The basic reproductive number, R0, is estimated at 3.0 (standard deviation 0.6) across all seasons and locations. The peak magnitude of RSV outbreaks is forecast with nearly 70% accuracy (i.e. nearly 70% of forecasts within 25% of the actual peak), four weeks before the predicted peak. This work represents a first step in the development of a real-time RSV prediction system. PMID:27716828

  16. Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Coyle Peter V

    2011-01-01

    Full Text Available Abstract Background Human respiratory syncytial virus (RSV causes severe respiratory disease in infants. Airway epithelial cells are the principle targets of RSV infection. However, the mechanisms by which it causes disease are poorly understood. Most RSV pathogenesis data are derived using laboratory-adapted prototypic strains. We hypothesized that such strains may be poorly representative of recent clinical isolates in terms of virus/host interactions in primary human bronchial epithelial cells (PBECs. Methods To address this hypothesis, we isolated three RSV strains from infants hospitalized with bronchiolitis and compared them with the prototypic RSV A2 in terms of cytopathology, virus growth kinetics and chemokine secretion in infected PBEC monolayers. Results RSV A2 rapidly obliterated the PBECs, whereas the clinical isolates caused much less cytopathology. Concomitantly, RSV A2 also grew faster and to higher titers in PBECs. Furthermore, dramatically increased secretion of IP-10 and RANTES was evident following A2 infection compared with the clinical isolates. Conclusions The prototypic RSV strain A2 is poorly representative of recent clinical isolates in terms of cytopathogenicity, viral growth kinetics and pro-inflammatory responses induced following infection of PBEC monolayers. Thus, the choice of RSV strain may have important implications for future RSV pathogenesis studies.

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

    Science.gov (United States)

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

    2016-05-01

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

  18. A Respiratory Syncytial Virus Replicon That Is Noncytotoxic and Capable of Long-Term Foreign Gene Expression▿

    OpenAIRE

    2011-01-01

    Respiratory syncytial virus (RSV) infection of most cultured cell lines causes cell-cell fusion and death. Cell fusion is caused by the fusion (F) glycoprotein and is clearly cytopathic, but other aspects of RSV infection may also contribute to cytopathology. To investigate this possibility, we generated an RSV replicon that lacks all three of its glycoprotein genes and so cannot cause cell-cell fusion or virus spread. This replicon includes a green fluorescent protein gene and an antibiotic ...

  19. Mammalian Cell-Derived Respiratory Syncytial Virus-Like Particles Protect the Lower as well as the Upper Respiratory Tract.

    Directory of Open Access Journals (Sweden)

    Pramila Walpita

    Full Text Available Globally, Respiratory Syncytial Virus (RSV is a leading cause of bronchiolitis and pneumonia in children less than one year of age and in USA alone, between 85,000 and 144,000 infants are hospitalized every year. To date, there is no licensed vaccine. We have evaluated vaccine potential of mammalian cell-derived native RSV virus-like particles (RSV VLPs composed of the two surface glycoproteins G and F, and the matrix protein M. Results of in vitro testing showed that the VLPs were functionally assembled and immunoreactive, and that the recombinantly expressed F protein was cleaved intracellularly similarly to the virus-synthesized F protein to produce the F1 and F2 subunits; the presence of the F1 fragment is critical for vaccine development since all the neutralizing epitopes present in the F protein are embedded in this fragment. Additional in vitro testing in human macrophage cell line THP-1 showed that both virus and the VLPs were sensed by TLR-4 and induced a Th1-biased cytokine response. Cotton rats vaccinated with RSV VLPs adjuvanted with alum and monophosphoryl lipid A induced potent neutralizing antibody response, and conferred protection in the lower as well as the upper respiratory tract based on substantial virus clearance from these sites. To the best of our knowledge, this is the first VLP/virosome vaccine study reporting protection of the lower as well as the upper respiratory tract: Prevention from replication in the nose is an important consideration if the target population is infants < 6 months of age. This is because continued virus replication in the nose results in nasal congestion and babies at this age are obligate nose breathers. In conclusion, these results taken together suggest that our VLPs show promise to be a safe and effective vaccine for RSV.

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

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    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.

  1. Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV Infection.

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    H K Brand

    Full Text Available Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making.In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort.Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4 as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age.By combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.

  2. Latitudinal variations in seasonal activity of influenza and respiratory syncytial virus (RSV: a global comparative review.

    Directory of Open Access Journals (Sweden)

    Kimberly Bloom-Feshbach

    Full Text Available There is limited information on influenza and respiratory syncytial virus (RSV seasonal patterns in tropical areas, although there is renewed interest in understanding the seasonal drivers of respiratory viruses.We review geographic variations in seasonality of laboratory-confirmed influenza and RSV epidemics in 137 global locations based on literature review and electronic sources. We assessed peak timing and epidemic duration and explored their association with geography and study settings. We fitted time series model to weekly national data available from the WHO influenza surveillance system (FluNet to further characterize seasonal parameters.Influenza and RSV activity consistently peaked during winter months in temperate locales, while there was greater diversity in the tropics. Several temperate locations experienced semi-annual influenza activity with peaks occurring in winter and summer. Semi-annual activity was relatively common in tropical areas of Southeast Asia for both viruses. Biennial cycles of RSV activity were identified in Northern Europe. Both viruses exhibited weak latitudinal gradients in the timing of epidemics by hemisphere, with peak timing occurring later in the calendar year with increasing latitude (P<0.03. Time series model applied to influenza data from 85 countries confirmed the presence of latitudinal gradients in timing, duration, seasonal amplitude, and between-year variability of epidemics. Overall, 80% of tropical locations experienced distinct RSV seasons lasting 6 months or less, while the percentage was 50% for influenza.Our review combining literature and electronic data sources suggests that a large fraction of tropical locations experience focused seasons of respiratory virus activity in individual years. Information on seasonal patterns remains limited in large undersampled regions, included Africa and Central America. Future studies should attempt to link the observed latitudinal gradients in

  3. Vertical transmission of respiratory syncytial virus modulates pre- and postnatal innervation and reactivity of rat airways.

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    Giovanni Piedimonte

    Full Text Available BACKGROUND: Environmental exposure to respiratory syncytial virus (RSV is a leading cause of respiratory infections in infants, but it remains unknown whether this infection is transmitted transplacentally from the lungs of infected mothers to the offspring. We sought to test the hypothesis that RSV travels from the respiratory tract during pregnancy, crosses the placenta to the fetus, persists in the lung tissues of the offspring, and modulates pre- and postnatal expression of growth factors, thereby predisposing to airway hyperreactivity. METHODOLOGY: Pregnant rats were inoculated intratracheally at midterm using recombinant RSV expressing red fluorescent protein (RFP. Viral RNA was amplified by RT-PCR and confirmed by sequencing. RFP expression was analyzed by flow cytometry and viral culture. Developmental and pathophysiologic implications of prenatal infection were determined by analyzing the expression of genes encoding critical growth factors, particularly neurotrophic factors and receptors. We also measured the expression of key neurotransmitters and postnatal bronchial reactivity in vertically infected lungs, and assessed their dependence on neurotrophic signaling using selective biological or chemical inhibition. PRINCIPAL FINDINGS: RSV genome was found in 30% of fetuses, as well as in the lungs of 40% of newborns and 25% of adults. RFP expression was also shown by flow cytometry and replicating virus was cultured from exposed fetuses. Nerve growth factor and its TrkA receptor were upregulated in RSV- infected fetal lungs and co-localized with increased cholinergic innervation. Acetylcholine expression and smooth muscle response to cholinergic stimulation increased in lungs exposed to RSV in utero and reinfected after birth, and blocking TrkA signaling inhibited both effects. CONCLUSIONS/SIGNIFICANCE: Our data show transplacental transmission of RSV from mother to offspring and persistence of vertically transmitted virus in lungs after

  4. 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

  5. Human CD8(+) T Cells Target Multiple Epitopes in Respiratory Syncytial Virus Polymerase.

    Science.gov (United States)

    Burbulla, Daniel; Günther, Patrick S; Peper, Janet K; Jahn, Gerhard; Dennehy, Kevin M

    2016-06-01

    Respiratory syncytial virus (RSV) infection is a serious health problem in young children, immunocompromised patients, and the elderly. The development of novel prevention strategies, such as a vaccine to RSV, is a high priority. One strategy is to design a peptide-based vaccine that activates appropriate CD8(+) T-cell responses. However, this approach is limited by the low number of RSV peptide epitopes defined to date that activate CD8(+) T cells. We aimed to identify peptide epitopes that are presented by common human leukocyte antigen types (HLA-A*01, -A*02, and -B*07). We identify one novel HLA-A*02-restricted and two novel HLA-A*01-restricted peptide epitopes from RSV polymerase. Peptide-HLA multimer staining of specific T cells from healthy donor peripheral blood mononuclear cell, the memory phenotype of such peptide-specific T cells ex vivo, and functional IFNγ responses in short-term stimulation assays suggest that these peptides are recognized during RSV infection. Such peptides are candidates for inclusion into a peptide-based RSV vaccine designed to stimulate defined CD8(+) T-cell responses.

  6. Human Respiratory Syncytial Virus: Role of Innate Immunity in Clearance and Disease Progression.

    Science.gov (United States)

    Farrag, Mohamed A; Almajhdi, Fahad N

    2016-01-01

    Human respiratory syncytial virus (HRSV) infections have worldwide records. The virus is responsible for bronchiolitis, pneumonia, and asthma in humans of different age groups. Premature infants, young children, and immunocompromised individuals are prone to severe HRSV infection that may lead to death. Based on worldwide estimations, millions of cases were reported in both developed and developing countries. In fact, HRSV symptoms develop mainly as a result of host immune response. Due to inability to establish long lasting adaptive immunity, HRSV infection is recurrent and hence impairs vaccine development. Once HRSV attached to the airway epithelia, interaction with the host innate immune components starts. HRSV interaction with pulmonary innate defenses is crucial in determining the disease outcome. Infection of alveolar epithelial cells triggers a cascade of events that lead to recruitment and activation of leukocyte populations. HRSV clearance is mediated by a number of innate leukocytes, including macrophages, natural killer cells, eosinophils, dendritic cells, and neutrophils. Regulation of these cells is mediated by cytokines, chemokines, and other immune mediators. Although the innate immune system helps to clear HRSV infection, it participates in disease progression such as bronchiolitis and asthma. Resolving the mechanisms by which HRSV induces pathogenesis, different possible interactions between the virus and immune components, and immune cells interplay are essential for developing new effective vaccines. Therefore, the current review focuses on how the pulmonary innate defenses mediate HRSV clearance and to what extent they participate in disease progression. In addition, immune responses associated with HRSV vaccines will be discussed.

  7. Group B strains of human respiratory syncytial virus in Saudi Arabia: molecular and phylogenetic analysis.

    Science.gov (United States)

    Almajhdi, Fahad N; Farrag, Mohamed A; Amer, Haitham M

    2014-04-01

    The genetic variability and circulation pattern of human respiratory syncytial virus group B (HRSV-B) strains, identified in Riyadh during the winters of 2008 and 2009, were evaluated by partial sequencing of the attachment (G) protein gene. The second hypervariable region (HVR-2) of G gene was amplified by RT-PCR, sequenced and compared to representatives of different HRSV-B genotypes. Sequence and phylogenetic analysis revealed that all Saudi strains belonged to the genotype BA, which is characterized by 60-nucleotide duplication at HVR-2. Only strains of 2008 were clustered with subgroup BA-IV, while those isolated at 2009 were clustered among the most recent subgroups (particularly BA-X and CB-B). Amino acid sequence analysis demonstrated 18 amino acid substitutions in Saudi HRSV-B strains; among which five are specific for individual strains. Furthermore, two potential N-glycosylation sites at residues 230 and 296 were identified for all Saudi strains, and an additional site at amino acid 273 was found only in Riyadh 28/2008 strain. O-glycosylation was predicted in 42-43 sites, where the majority (no = 38) are highly conserved among Saudi strains. The average ratio between non-synonymous and synonymous mutations (ω) implied stabilizing selection pressure on G protein, with evidences of positive selection on certain Saudi strains. This report provides preliminary data on the circulation pattern and molecular characteristics of HRSV-B strains circulating in Saudi Arabia.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    OBJECTIVE: To assess the risk and risk factors for respiratory syncytial virus (RSV) hospitalisation and determinants of the severity of RSV disease in children with heart disease. METHODS: By using a database on RSV tests in Denmark all children with RSV diagnosed with heart disease in Denmark...... from January 1996 to April 2003 were identified. For each case child one control child matched for age and centre was drawn from the population of children with heart disease. Clinical information was obtained through a review of all records. RESULTS: Data were obtained on 313 pairs. Median age...... at admission was 280 days (range 15-2379). In the multivariate analysis predictors of RSV hospitalisation were Down syndrome (odds ratio (OR) 3.24, 95% CI 1.80 to 5.80), cardiomyopathy (OR 5.84, 95% CI 1.26 to 27.16) and haemodynamically significant heart disease (OR 1.53, 95% CI 1.04 to 2.26). During RSV...

  9. A recombinant varicella vaccine harboring a respiratory syncytial virus gene induces humoral immunity.

    Science.gov (United States)

    Murakami, Kouki; Matsuura, Masaaki; Ota, Megumi; Gomi, Yasuyuki; Yamanishi, Koichi; Mori, Yasuko

    2015-11-09

    The varicella-zoster virus (VZV) Oka vaccine strain (vOka) is highly efficient and causes few adverse events; therefore, it is used worldwide. We previously constructed recombinant vOka (rvOka) harboring the mumps virus gene. Immunizing guinea pigs with rvOka induced the production of neutralizing antibodies against the mumps virus and VZV. Here, we constructed recombinant vOka viruses containing either the respiratory syncytial virus (RSV) subgroup A fusion glycoprotein (RSV A-F) gene or RSV subgroup B fusion glycoprotein (RSV B-F) gene (rvOka-RSV A-F or rvOka-RSV B-F). Indirect immunofluorescence and Western blot analyses confirmed the expression of each recombinant RSV protein in virus-infected cells. Immunizing guinea pigs with rvOka-RSV A-F or rvOka-RSV B-F led to the induction of antibodies against RSV proteins. These results suggest that the current varicella vaccine genome can be used to generate custom-made vaccine vectors to develop the next generation of live vaccines.

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

    Directory of Open Access Journals (Sweden)

    Hodemaekers Hennie M

    2011-09-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the most common cause of bronchiolitis in infants. Following RSV bronchiolitis, 50% of children develop post-bronchiolitis wheeze (PBW. Animal studies have suggested that interleukin (IL-10 plays a critical role in the pathogenesis of RSV bronchiolitis and subsequent airway hyperresponsiveness. Previously, we showed that ex vivo monocyte IL-10 production is a predictor of PBW. Additionally, heterozygosity of the single-nucleotide polymorphism (SNP rs1800872 in the IL10 promoter region was associated with protection against RSV bronchiolitis. Methods This study aimed to determine the in vivo role of IL-10 in RSV pathogenesis and recurrent wheeze in a new cohort of 235 infants hospitalized for RSV bronchiolitis. IL-10 levels in nasopharyngeal aspirates (NPAs were measured at the time of hospitalization and the IL10 SNP rs1800872 genotype was determined. Follow-up data were available for 185 children (79%. Results Local IL-10 levels during RSV infection turned out to be higher in infants that later developed physician diagnosed PBW as compared to infants without PBW in the first year after RSV infection (958 vs 692 pg/ml, p = 0.02. The IL10 promoter SNP rs1800872 was not associated with IL-10 concentration in NPAs. Conclusion The relationship between high local IL-10 levels during the initial RSV infection and physician diagnosed PBW provides further evidence of the importance of the IL-10 response during RSV bronchiolitis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Alsuwaidi, Ahmed R., E-mail: alsuwaidia@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Albawardi, Alia, E-mail: alia.albawardi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Almarzooqi, Saeeda, E-mail: saeeda.almarzooqi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Benedict, Sheela, E-mail: sheela.benedict@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Othman, Aws R., E-mail: aws.rashad@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Hartwig, Stacey M., E-mail: stacey-hartwig@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Varga, Steven M., E-mail: steven-varga@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Souid, Abdul-Kader, E-mail: asouid@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates)

    2014-04-15

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

  12. The respiratory syncytial virus nucleoprotein-RNA complex forms a left-handed helical nucleocapsid.

    Science.gov (United States)

    Bakker, Saskia E; Duquerroy, Stéphane; Galloux, Marie; Loney, Colin; Conner, Edward; Eléouët, Jean-François; Rey, Félix A; Bhella, David

    2013-08-01

    Respiratory syncytial virus (RSV) is an important human pathogen. Its nucleocapsid (NC), which comprises the negative sense RNA viral genome coated by the viral nucleoprotein N, is a critical assembly that serves as template for both mRNA synthesis and genome replication. We have previously described the X-ray structure of an NC-like structure: a decameric ring formed of N-RNA that mimics one turn of the helical NC. In the absence of experimental data we had hypothesized that the NC helix would be right-handed, as the N-N contacts in the ring appeared to more easily adapt to that conformation. We now unambiguously show that the RSV NC is a left-handed helix. We further show that the contacts in the ring can be distorted to maintain key N-N-protein interactions in a left-handed helix, and discuss the implications of the resulting atomic model of the helical NC for viral replication and transcription.

  13. An attraction-repulsion point process model for respiratory syncytial virus infections.

    Science.gov (United States)

    Goldstein, Joshua; Haran, Murali; Simeonov, Ivan; Fricks, John; Chiaromonte, Francesca

    2015-06-01

    How is the progression of a virus influenced by properties intrinsic to individual cells? We address this question by studying the susceptibility of cells infected with two strains of the human respiratory syncytial virus (RSV-A and RSV-B) in an in vitro experiment. Spatial patterns of infected cells give us insight into how local conditions influence susceptibility to the virus. We observe a complicated attraction and repulsion behavior, a tendency for infected cells to lump together or remain apart. We develop a new spatial point process model to describe this behavior. Inference on spatial point processes is difficult because the likelihood functions of these models contain intractable normalizing constants; we adapt an MCMC algorithm called double Metropolis-Hastings to overcome this computational challenge. Our methods are computationally efficient even for large point patterns consisting of over 10,000 points. We illustrate the application of our model and inferential approach to simulated data examples and fit our model to various RSV experiments. Because our model parameters are easy to interpret, we are able to draw meaningful scientific conclusions from the fitted models.

  14. A Classification Study of Respiratory Syncytial Virus (RSV Inhibitors by Variable Selection with Random Forest

    Directory of Open Access Journals (Sweden)

    Shuwei Zhang

    2011-02-01

    Full Text Available Experimental pEC50s for 216 selective respiratory syncytial virus (RSV inhibitors are used to develop classification models as a potential screening tool for a large library of target compounds. Variable selection algorithm coupled with random forests (VS-RF is used to extract the physicochemical features most relevant to the RSV inhibition. Based on the selected small set of descriptors, four other widely used approaches, i.e., support vector machine (SVM, Gaussian process (GP, linear discriminant analysis (LDA and k nearest neighbors (kNN routines are also employed and compared with the VS-RF method in terms of several of rigorous evaluation criteria. The obtained results indicate that the VS-RF model is a powerful tool for classification of RSV inhibitors, producing the highest overall accuracy of 94.34% for the external prediction set, which significantly outperforms the other four methods with the average accuracy of 80.66%. The proposed model with excellent prediction capacity from internal to external quality should be important for screening and optimization of potential RSV inhibitors prior to chemical synthesis in drug development.

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

    Science.gov (United States)

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

    2015-08-01

    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.

  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. Respiratory syncytial virus assembles into structured filamentous virion particles independently of host cytoskeleton and related proteins.

    Directory of Open Access Journals (Sweden)

    Fyza Y Shaikh

    Full Text Available Respiratory syncytial virus (RSV is a single-stranded RNA virus that assembles into viral filaments at the cell surface. Virus assembly often depends on the ability of a virus to use host proteins to accomplish viral tasks. Since the fusion protein cytoplasmic tail (FCT is critical for viral filamentous assembly, we hypothesized that host proteins important for viral assembly may be recruited by the FCT. Using a yeast two-hybrid screen, we found that filamin A interacted with FCT, and mammalian cell experiments showed it localized to viral filaments but did not affect viral replication. Furthermore, we found that a number of actin-associated proteins also were excluded from viral filaments. Actin or tubulin cytoskeletal rearrangement was not necessary for F trafficking to the cell surface or for viral assembly into filaments, but was necessary for optimal viral replication and may be important for anchoring viral filaments. These findings suggest that RSV assembly into filaments occurs independently of actin polymerization and that viral proteins are the principal drivers for the mechanical tasks involved with formation of complex, structured RSV filaments at the host cell plasma membrane.

  18. Direct Inhibition of Cellular Fatty Acid Synthase Impairs Replication of Respiratory Syncytial Virus and Other Respiratory Viruses.

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    Yamini M Ohol

    Full Text Available Fatty acid synthase (FASN catalyzes the de novo synthesis of palmitate, a fatty acid utilized for synthesis of more complex fatty acids, plasma membrane structure, and post-translational palmitoylation of host and viral proteins. We have developed a potent inhibitor of FASN (TVB-3166 that reduces the production of respiratory syncytial virus (RSV progeny in vitro from infected human lung epithelial cells (A549 and in vivo from mice challenged intranasally with RSV. Addition of TVB-3166 to the culture medium of RSV-infected A549 cells reduces viral spread without inducing cytopathic effects. The antiviral effect of the FASN inhibitor is a direct consequence of reducing de novo palmitate synthesis; similar doses are required for both antiviral activity and inhibition of palmitate production, and the addition of exogenous palmitate to TVB-3166-treated cells restores RSV production. TVB-3166 has minimal effect on RSV entry but significantly reduces viral RNA replication, protein levels, viral particle formation and infectivity of released viral particles. TVB-3166 substantially impacts viral replication, reducing production of infectious progeny 250-fold. In vivo, oral administration of TVB-3166 to RSV-A (Long-infected BALB/c mice on normal chow, starting either on the day of infection or one day post-infection, reduces RSV lung titers 21-fold and 9-fold respectively. Further, TVB-3166 also inhibits the production of RSV B, human parainfluenza 3 (PIV3, and human rhinovirus 16 (HRV16 progeny from A549, HEp2 and HeLa cells respectively. Thus, inhibition of FASN and palmitate synthesis by TVB-3166 significantly reduces RSV progeny both in vitro and in vivo and has broad-spectrum activity against other respiratory viruses. FASN inhibition may alter the composition of regions of the host cell membrane where RSV assembly or replication occurs, or change the membrane composition of RSV progeny particles, decreasing their infectivity.

  19. Respiratory syncytial virus infection in children under one year of age hospitalized for acute respiratory diseases in Pelotas, RS

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    Silvia Elaine Cardozo Macedo

    2003-01-01

    Full Text Available INTRODUCTION: Acute respiratory diseases (ARDs are a major cause of infant morbidity and mortality. OBJECTIVE: The present case-controlled study investigated the hospitalizations by ARDs in children under one year of age and the association with the respiratory syncytial virus (RSV in za Pelotas, RS. METHODS: All children under one year of age hospitalized due to ARDs from August 1997 to July of 1998 were followed-up in the four hospitals of the city. A standardized questionnaire was applied to the children's mother regarding symptoms of the actual illness in addition to social and demographic variables, nutrition, and previous morbidity. The final diagnosis of ARDs was performed by an arbiter (a pediatrician based on the hospital records of the children and the data on the questionnaire. Nasopharyngeal secretions were collected for RSV detection by direct immunofluorescence. RESULTS: The study included 650 children and the annual incidence rate of hospital admissions for ARDs was 13.9%. Admissions showed a seasonal pattern with most of the hospitalizations occurring from July to October. The main causes of admission were: pneumonia (43.7%, bronchiolitis (31.0%, asthma (20.3%, influenza (3.5%, otitis media (0.8% and laryngitis (0.6%. The overall prevalence of RSV was 30.7%, with 40.2% in bronchiolitis, 28.6% in influenza, 27.4% in asthma, 26.3% in pneumonia, and 25% in otitis media. CONCLUSIONS: The results of the present study confirm the high morbidity of ARDs in childhood and the seasonal pattern of ARDs hospitalizations and their association with RSV infection.

  20. Marked induction of matrix metalloproteinase-10 by respiratory syncytial virus infection in human nasal epithelial cells.

    Science.gov (United States)

    Hirakawa, Satoshi; Kojima, Takashi; Obata, Kazufumi; Okabayashi, Tamaki; Yokota, Shin-Ichi; Nomura, Kazuaki; Obonai, Toshimasa; Fuchimoto, Jun; Himi, Tetsuo; Tsutsumi, Hiroyuki; Sawada, Norimasa

    2013-12-01

    Respiratory syncytial virus (RSV) is an important pathogen of bronchiolitis, asthma, and severe lower respiratory tract disease in infants and young children. Matrix metalloproteinases (MMPs) play key roles in viral infection, inflammation and remodeling of the airway. However, the roles and regulation of MMPs in human nasal epithelial cells (HNECs) after RSV infection remain unclear. To investigate the regulation of MMP induced after RSV infection in HNECs, an RSV-infected model of HNECs in vitro was used. It was found that mRNA of MMP-10 was markedly increased in HNECs after RSV infection, together with induction of mRNAs of MMP-1, -7, -9, and -19. The amount of MMP-10 released from HNECs was also increased in a time-dependent manner after RSV infection as was that of chemokine RANTES. The upregulation of MMP-10 in HNECs after RSV infection was prevented by inhibitors of NF-κB and pan-PKC with inhibition of RSV replication, whereas it was prevented by inhibitors of JAK/STAT, MAPK, and EGF receptors without inhibition of RSV replication. In lung tissue of an infant with severe RSV infection in which a few RSV antibody-positive macrophages were observed, MMP-10 was expressed at the apical side of the bronchial epithelial cells and alveolar epithelial cells. In conclusion, MMP-10 induced by RSV infection in HNECs is regulated via distinct signal transduction pathways with or without relation to RSV replication. MMP-10 may play an important role in the pathogenesis of RSV diseases and it has the potential to be a novel marker and therapeutic target for RSV infection.

  1. Weaning infants with respiratory syncytial virus from mechanical ventilation through a fuzzy-logic controller.

    Science.gov (United States)

    Olliver, S; Davis, G M; Hatzakis, G E

    2003-01-01

    We have previously developed a fuzzy logic controller for weaning adults with chronic obstructive pulmonary disease using pressure support ventilation (PSV). We used the core of our fuzzy logic-based weaning platform and further developed parametrizable components for weaning newborns of differing body size and disease-state. The controller was validated on neonates recovering from congenital heart disease (CHD) while receiving synchronous intermittent mandatory ventilation (SIMV). We wished to compare the efficacy of this controller versus the bedside weaning protocol in children with respiratory syncytial virus pneumonitis/bronchiolitis (RSV) in the pediatric intensive care unit (PICU). The fuzzy controller evaluated the "current" and "trend" weaning status of the newborn to quantitatively determine the change in the SIMV integrated ventilatory setting. For the "current" status it used heart rate (HR), respiratory rate (RR), tidal volume (VT) and oxygen saturation (SaO2), while for the "trend" status the differences of deltaRR/ deltat, deltaHR/ deltat, and deltaSaO2/ deltat recorded between two subsequent time points were utilized. The enumerated vital signs were fuzzified and then probability levels of occurrence were assigned. Individualized "golden" goals for SaO2 were set for each newborn. We retrospectively assessed the charts of 19 newborns, 113+/-128 days old, 5,546+/-2,321 gr body weight, weaning for 99+/-46 days, at 2-hour intervals. The SIMV levels proposed by the fuzzy controller were matched to those levels actually applied. In 60% of the time both values coincided. For the remaining 40%, the controller was more aggressive suggesting lower values of SIMV than the applied ones. The Area under the SIMV curves over time was 1,969+/-1,044 for the applied vs 1,886+/-978 for the suggested levels, respectively. The fuzzy controller adjusted for body size and disease-pattern can approximate the actual weaning course of newborns with RSV.

  2. The impact of viral dynamics on the clinical severity of infants with respiratory syncytial virus bronchiolitis.

    Science.gov (United States)

    Zhou, Lili; Xiao, Qiuyan; Zhao, Yao; Huang, Ailong; Ren, Luo; Liu, Enmei

    2015-08-01

    The impact of dynamic respiratory syncytial virus (RSV) load on the clinical severity of hospitalized infants with bronchiolitis has not been clarified. Nasopharyngeal aspirates were obtained from 60 infants who were diagnosed with bronchiolitis within 96 hr of wheezing onset upon admission and on days 3, 5, and 7 in the hospital, and 17 respiratory viruses were detected. The RSV load was quantified by real-time qPCR for RSV subtypes A and B at different time points. Scoring criteria were used to evaluate the degree of severity. A total of 40 infants were determined to be RSV-positive, nine were identified as RSV subtype A (RSVA), and 31 were RSV subtype B (RSVB). The peak RSV load was observed upon admission, and the RSV load decreased significantly over time; in addition, this decrease began to have significant differences on day 5. There was a positive correlation between the RSV load and the clinical score (r(2)  = 0.121 and P < 0.001). According to the clinical scores, the infants in the severe group tended to have higher RSV loads than those in the moderate and mild groups. Multivariate logistic regression models revealed that the viral load on day 3 was independently associated with the degree of severity. This study elucidated that a higher mean RSV load was associated with a more severe disease and a longer duration of hospitalization and symptoms. This study also clarified RSV replication in infants and provides a theoretical basis for specifying an anti-RSV therapy strategy.

  3. Respiratory syncytial virus fusion protein promotes TLR-4-dependent neutrophil extracellular trap formation by human neutrophils.

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    Giselle A Funchal

    Full Text Available Acute viral bronchiolitis by Respiratory Syncytial Virus (RSV is the most common respiratory illness in children in the first year of life. RSV bronchiolitis generates large numbers of hospitalizations and an important burden to health systems. Neutrophils and their products are present in the airways of RSV-infected patients who developed increased lung disease. Neutrophil Extracellular Traps (NETs are formed by the release of granular and nuclear contents of neutrophils in the extracellular space in response to different stimuli and recent studies have proposed a role for NETs in viral infections. In this study, we show that RSV particles and RSV Fusion protein were both capable of inducing NET formation by human neutrophils. Moreover, we analyzed the mechanisms involved in RSV Fusion protein-induced NET formation. RSV F protein was able to induce NET release in a concentration-dependent fashion with both neutrophil elastase and myeloperoxidase expressed on DNA fibers and F protein-induced NETs was dismantled by DNase treatment, confirming that their backbone is chromatin. This viral protein caused the release of extracellular DNA dependent on TLR-4 activation, NADPH Oxidase-derived ROS production and ERK and p38 MAPK phosphorylation. Together, these results demonstrate a coordinated signaling pathway activated by F protein that led to NET production. The massive production of NETs in RSV infection could aggravate the inflammatory symptoms of the infection in young children and babies. We propose that targeting the binding of TLR-4 by F protein could potentially lead to novel therapeutic approaches to help control RSV-induced inflammatory consequences and pathology of viral bronchiolitis.

  4. Respiratory syncytial virus-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.)

  5. NGF is an essential survival factor for bronchial epithelial cells during respiratory syncytial virus infection.

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    Sreekumar Othumpangat

    Full Text Available Overall expression of neurotrophins in the respiratory tract is upregulated in infants infected by the respiratory syncytial virus (RSV, but it is unclear where (structural vs. inflammatory cells, upper vs. lower airways and why, these changes occur. We analyzed systematically the expression of neurotrophic factors and receptors following RSV infection of human nasal, tracheal, and bronchial epithelial cells, and tested the hypothesis that neurotrophins work as innate survival factors for infected respiratory epithelia.Expression of neurotrophic factors (nerve growth factor, NGF; brain-derived neurotrophic factor, BDNF and receptors (trkA, trkB, p75 was analyzed at the protein level by immunofluorescence and flow cytometry and at the mRNA level by real-time PCR. Targeted siRNA was utilized to blunt NGF expression, and its effect on virus-induced apoptosis/necrosis was evaluated by flow cytometry following annexin V/7-AAD staining.RSV infection was more efficient in cells from more distal (bronchial vs. more proximal origin. In bronchial cells, RSV infection induced transcript and protein overexpression of NGF and its high-affinity receptor trkA, with concomitant downregulation of the low-affinity p75(NTR. In contrast, tracheal cells exhibited an increase in BDNF, trkA and trkB, and nasal cells increased only trkA. RSV-infected bronchial cells transfected with NGF-specific siRNA exhibited decreased trkA and increased p75(NTR expression. Furthermore, the survival of bronchial epithelial cells was dramatically decreased when their endogenous NGF supply was depleted prior to RSV infection.RSV infection of the distal airway epithelium, but not of the more proximal sections, results in overexpression of NGF and its trkA receptor, while the other p75(NTR receptor is markedly downregulated. This pattern of neurotrophin expression confers protection against virus-induced apoptosis, and its inhibition amplifies programmed cell death in the infected

  6. Respiratory syncytial virus outbreak in neonatal intensive care unit: Impact of infection control measures plus palivizumab use

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    Silva Camila de A

    2012-05-01

    Full Text Available Abstract Background The occurrence of a respiratory syncytial virus (RSV outbreak in a Neonatal Intensive Care Unit (NICU is related to unfavorable outcomes, as this infection can lead to respiratory distress and death in premature in infants. Report the successful control of an outbreak that occurred in April 2010 in a NICU. Methods After the index case, of 18 premature infants placed in the same room 10 infants were infected. Of those 10, 6 developed mild to moderate respiratory symptoms, 4 persisted asymptomatic and no death occurred. Contact and respiratory precautions were rapidly initiated, the infants were cohorted in 3 different rooms and palivizumab was administered to all contacts. Results The outbreak was controlled and no new cases were subsequently indentified. Conclusion Standard infection control measures plus palivizumab prophylaxis were efficient in rapid control of the outbreak.

  7. Induction of mucosal and systemic immunity against respiratory syncytial virus by inactivated virus supplemented with TLR9 and NOD2 ligands

    NARCIS (Netherlands)

    Shafique, Muhammad; Wilschut, Jan; de Haan, Aalzen

    2012-01-01

    Respiratory syncytial virus (RSV) infection is the most important viral cause of severe respiratory disease in infants and children worldwide and also forms a serious threat in the elderly. The development of RSV vaccine, however, has been hampered by the disastrous outcome of an earlier trial using

  8. Recombinant subgroup B human respiratory syncytial virus expressing enhanced green fluorescent protein efficiently replicates in primary human cells and is virulent in cotton rats

    NARCIS (Netherlands)

    K. Lemon (Ken); D.T. Nguyen (Tien); M. Ludlow (Martin); L.J. Rennick (Linda); S. Yüksel (Selma); G. van Amerongen (Geert); S. McQuaid (Stephen); B.K. Rima (Bert); R.L. de Swart (Rik); W.P. Duprex (Paul)

    2015-01-01

    textabstractHuman respiratory syncytial virus (HRSV) is the most important viral cause of severe respiratory tract disease in infants. Two subgroups (A and B) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. Existing in vitro

  9. A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Høgh, Mette; Nordbø, Svein;

    2008-01-01

    Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are important respiratory pathogens with similar symptomatology. The aim of this prospective birth cohort study was to identify risk factors for an hMPV or RSV infection during the first year of life in unselected healthy children...

  10. Differential expression of cytokines in response to respiratory syncytial virus infection of calves with high or low circulating 25-hydroxyvitamin D3

    Science.gov (United States)

    Deficiency of serum levels of 25-hydroxyvitamin D3 has been related to increased risk of lower respiratory tract infections (LRTI) in children. Respiratory syncytial virus (RSV) is the leading cause of LRTI in infants and young children. The neonatal calf model of RSV infection shares many features ...

  11. Respiratory system mechanics in patients receiving aerosolized ribavirin during mechanical ventilation for suspected respiratory syncytial viral infection.

    Science.gov (United States)

    Jefferson, L S; Coss-Bu, J A; Englund, J A; Walding, D; Stein, F

    1999-08-01

    Respiratory syncytial virus (RSV) is an important respiratory pathogen for infants. Aerosolized ribavirin (AR) has been used in mechanically ventilated (MV) patients with RSV bronchiolitis. The purpose of this study was to measure respiratory system mechanics (RSM) in pediatric patients requiring MV and receiving AR for suspected RSV. Patients were prospectively randomized to receive AR, either at a regular dose (RD) (6 g/300 mL over 18 hr/day) or a high dose (HD) (6 g/100 mL over 2 hr, three times a day). To measure changes in RSM, a passive exhalation technique was used before and after each dose of AR; time constant (tc) in s, resistance (Rrs) in cmH(2)O/mL/kg/s, and quasistatic compliance (Crs) in mL/cmH(2)O/kg were measured. Airway pressure and flow signals were obtained and analyzed using a pneumotachograph, a differential pressure transducer, and a computer interface. Statistical analysis was done by Mann-Whitney and Wilcoxon rank tests. Thirteen patients were enrolled: 5 patients in the HD group (mean age of 52 months), and 8 patients in the RD group (mean age of 10 months). Four and 5 patients were positive for RSV by ELISA in the HD and RD groups, respectively. The RSM in the HD group were: tc, 0.58 +/- 0.15 s and 0.55 +/- 0.20 s before and after AR, respectively; Rrs, 0.03 +/- 0. 03 cmH(2)0/mL/kg/s and 0.02 +/- 0.02 cmH(2)0/mL/kg/s, respectively; and Crs, 0.63 +/- 0.21 mL/cmH(2)O/kg and 0.70 +/- 0.13 mL/cmH(2)O/kg, respectively. In the RD group, the RSM were: tc, 0.37 +/- 0.12 s and 0.31 +/- 0.10 s before and after AR, respectively; Rrs, 0.03 +/- 0.02 cmH(2)0/mL/kg/s and 0.02 +/- 0.01 cmH(2)0/mL/kg/s, respectively (P mechanical ventilation does not worsen RSM.

  12. Mannheimia haemolytica biofilm formation on bovine respiratory epithelial cells.

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    Boukahil, Ismail; Czuprynski, Charles J

    2016-12-25

    Mannheimia haemolytica is the most important bacterial agent associated with the bovine respiratory disease complex (BRDC), which causes worldwide economic losses to the cattle industry. M. haemolytica cells initially colonize the tonsillar crypts in the upper respiratory tract of cattle, from where they can subsequently descend into the lungs to cause disease. Many bacteria exist as biofilms inside their hosts. We hypothesize that M. haemolytica colonization of cattle during its commensal state may include biofilm formation. To begin to assess this possibility, we developed an in vitro system to study biofilm formation directly on bovine respiratory epithelial cells. Using fixed primary bovine bronchial epithelial cells, we observed M. haemolytica biofilm formation after a 48h incubation period at 37°C. Addition of mucin, the main component of mucus present in the upper respiratory tract, decreased M. haemolytica biofilm formation on bovine epithelial cells. We investigated the effects of prior viral infection of the epithelial cells on subsequent biofilm formation by M. haemolytica and found negligible effects. Utilization of this model system will provide new insights into the potential role of biofilm formation by M. haemolytica in the pathogenesis of BRDC.

  13. Respiratory Syncytial Virus Persistence in Murine Macrophages Impairs IFN-β Response but Not Synthesis

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    Evelyn Rivera-Toledo

    2015-10-01

    Full Text Available Type-I interferon (IFN-I production is an early response to viral infection and pathogenic viruses have evolved multiple strategies to evade this cellular defense. Some viruses can establish and maintain persistent infections by altering the IFN-I signaling pathway. Here, we studied IFN-I synthesis and response in an in vitro model of persistent infection by respiratory syncytial virus (RSV in a murine macrophage-like cell line. In this model, interferon regulatory factor 3 was constitutively active and located at nuclei of persistently infected cells, inducing expression of IFN-beta mRNA and protein. However, persistently infected macrophages did not respond in an autocrine manner to the secreted-IFN-beta or to recombinant-IFN-beta, since phosphorylated-STAT1 was not detected by western blot and transcription of the interferon-stimulated genes (ISGs Mx1 and ISG56 was not induced. Treatment of non-infected macrophages with supernatants from persistently infected cells induced STAT1 phosphorylation and ISGs expression, mediated by the IFN-I present in the supernatants, because blocking the IFN-I receptor inhibited STAT1 phosphorylation. Results suggest that the lack of autocrine response to IFN-I by the host cell may be one mechanism for maintenance of RSV persistence. Furthermore, STAT1 phosphorylation and ISGs expression induced in non-infected cells by supernatants from persistently infected macrophages suggest that RSV persistence may trigger a proinflammatory phenotype in non-infected cells as part of the pathogenesis of RSV infection.

  14. Sub-nucleocapsid nanoparticles: a nasal vaccine against respiratory syncytial virus.

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    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.

  15. Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis

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    Skjaeret Camilla

    2006-12-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a major cause of viral bronchiolitis in infants worldwide, and environmental, viral and host factors are all of importance for disease susceptibility and severity. To study the systemic host response to this disease we used the microarray technology to measure mRNA gene expression levels in whole blood of five male infants hospitalised with acute RSV, subtype B, bronchiolitis versus five one year old male controls exposed to RSV during infancy without bronchiolitis. The gene expression levels were further evaluated in a new experiment using quantitative real-time polymerase chain reaction (QRT-PCR both in the five infants selected for microarray and in 13 other infants hospitalised with the same disease. Results Among the 30 genes most differentially expressed by microarray nearly 50% were involved in immunological processes. We found the highly upregulated interferon, alpha-inducible protein 27 (IFI27 and the highly downregulated gene Charcot-Leyden crystal protein (CLC to be the two most differentially expressed genes in the microarray study. When performing QRT-PCR on these genes IFI27 was upregulated in all but one infant, and CLC was downregulated in all 18 infants, and similar to that given by microarray. Conclusion The gene IFI27 is upregulated and the gene CLC is downregulated in whole blood of infants hospitalised with RSV, subtype B, bronchiolitis and is not reported before. More studies are needed to elucidate the specificity of these gene expressions in association with host response to this virus in bronchiolitis of moderate severity.

  16. A Cysteine Zipper Stabilizes a Pre-Fusion F Glycoprotein Vaccine for Respiratory Syncytial Virus.

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    Guillaume B E Stewart-Jones

    Full Text Available Recombinant subunit vaccines should contain minimal non-pathogen motifs to reduce potential off-target reactivity. We recently developed a vaccine antigen against respiratory syncytial virus (RSV, which comprised the fusion (F glycoprotein stabilized in its pre-fusion trimeric conformation by "DS-Cav1" mutations and by an appended C-terminal trimerization motif or "foldon" from T4-bacteriophage fibritin. Here we investigate the creation of a cysteine zipper to allow for the removal of the phage foldon, while maintaining the immunogenicity of the parent DS-Cav1+foldon antigen. Constructs without foldon yielded RSV F monomers, and enzymatic removal of the phage foldon from pre-fusion F trimers resulted in their dissociation into monomers. Because the native C terminus of the pre-fusion RSV F ectodomain encompasses a viral trimeric coiled-coil, we explored whether introduction of cysteine residues capable of forming inter-protomer disulfides might allow for stable trimers. Structural modeling indicated the introduced cysteines to form disulfide "rings", with each ring comprising a different set of inward facing residues of the coiled-coil. Three sets of rings could be placed within the native RSV F coiled-coil, and additional rings could be added by duplicating portions of the coiled-coil. High levels of neutralizing activity in mice, equivalent to that of the parent DS-Cav1+foldon antigen, were elicited by a 4-ring stabilized RSV F trimer with no foldon. Structure-based alteration of a viral coiled-coil to create a cysteine zipper thus allows a phage trimerization motif to be removed from a candidate vaccine antigen.

  17. Pharyngeal microflora disruption by antibiotics promotes airway hyperresponsiveness after respiratory syncytial virus infection.

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    Ke Ni

    Full Text Available BACKGROUND: Regulatory T cells (Treg cells, which are essential for regulation of immune response to respiratory syncytial virus (RSV infection, are promoted by pharyngeal commensal pneumococcus. The effects of pharyngeal microflora disruption by antibiotics on airway responsiveness and relative immune responses after RSV infection have not been clarified. METHODS: Female BALB/c mice (aged 3 weeks were infected with RSV and then treated with either oral antibiotics or oral double distilled water (ddH(2O from 1 d post infection (pi. Changes in pharyngeal microflora were analyzed after antibiotic treatment for 7 d and 14 d. At 8 d pi and 15 d pi, the inflammatory cells in bronchoalveolar lavage fluid (BALF were investigated in combination with tests of pulmonary histopathology, airway hyperresponsiveness (AHR, pulmonary and splenic Treg cells responses. Pulmonary Foxp3 mRNA expression, IL-10 and TGF-β1 in BALF and lung homogenate were investigated at 15 d pi. Ovalbumin (OVA challenge was used to induce AHR after RSV infection. RESULTS: The predominant pharyngeal commensal, Streptococcus, was cleared by antibiotic treatment for 7 d. Same change also existed after antibiotic treatment for 14 d. After RSV infection, AHR was promoted by antibiotic treatment at 15 d pi. Synchronous decreases of pulmonary Treg cells, Foxp3 mRNA and TGF-β1 were detected. Similar results were observed under OVA challenge. CONCLUSIONS: After RSV infection, antibiotic treatment cleared pharyngeal commensal bacteria such as Streptococcus, which consequently, might induce AHR and decrease pulmonary Treg cells.

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

    Science.gov (United States)

    Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

    2014-01-01

    We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

  19. Duration of shedding of respiratory syncytial virus in a community study of Kenyan children

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    Ngama Mwanajuma

    2010-01-01

    Full Text Available Abstract Background Our understanding of the transmission dynamics of respiratory syncytial virus (RSV infection will be better informed with improved data on the patterns of shedding in cases not limited only to hospital admissions. Methods In a household study, children testing RSV positive by direct immunofluorescent antibody test (DFA were enrolled. Nasal washings were scheduled right away, then every three days until day 14, every 7 days until day 28 and every 2 weeks until a maximum of 16 weeks, or until the first DFA negative RSV specimen. The relationship between host factors, illness severity and viral shedding was investigated using Cox regression methods. Results From 151 families a total of 193 children were enrolled with a median age of 21 months (range 1-164 months, 10% infants and 46% male. The rate of recovery from infection was 0.22/person/day (95% CI 0.19-0.25 equivalent to a mean duration of shedding of 4.5 days (95%CI 4.0-5.3, with a median duration of shedding of 4 days (IQR 2-6, range 1-14. Children with a history of RSV infection had a 40% increased rate of recovery i.e. shorter duration of viral shedding (hazard ratio 1.4, 95% CI 1.01-1.86. The rate of cessation of shedding did not differ significantly between males and females, by severity of infection or by age. Conclusion We provide evidence of a relationship between the duration of shedding and history of infection, which may have a bearing on the relative role of primary versus re-infections in RSV transmission in the community.

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

    Directory of Open Access Journals (Sweden)

    Songhui Zhai

    2016-09-01

    Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Respiratory Syncytial Virus Induces Host RNA Stress Granules To Facilitate Viral Replication▿

    Science.gov (United States)

    Lindquist, Michael E.; Lifland, Aaron W.; Utley, Thomas J.; Santangelo, Philip J.; Crowe, James E.

    2010-01-01

    Mammalian cell cytoplasmic RNA stress granules are induced during various conditions of stress and are strongly associated with regulation of host mRNA translation. Several viruses induce stress granules during the course of infection, but the exact function of these structures during virus replication is not well understood. In this study, we showed that respiratory syncytial virus (RSV) induced host stress granules in epithelial cells during the course of infection. We also showed that stress granules are distinct from cytoplasmic viral inclusion bodies and that the RNA binding protein HuR, normally found in stress granules, also localized to viral inclusion bodies during infection. Interestingly, we demonstrated that infected cells containing stress granules also contained more RSV protein than infected cells that did not form inclusion bodies. To address the role of stress granule formation in RSV infection, we generated a stable epithelial cell line with reduced expression of the Ras-GAP SH3 domain-binding protein (G3BP) that displayed an inhibited stress granule response. Surprisingly, RSV replication was impaired in these cells compared to its replication in cells with intact G3BP expression. In contrast, knockdown of HuR by RNA interference did not affect stress granule formation or RSV replication. Finally, using RNA probes specific for RSV genomic RNA, we found that viral RNA predominantly localized to viral inclusion bodies but a small percentage also interacted with stress granules during infection. These results suggest that RSV induces a host stress granule response and preferentially replicates in host cells that have committed to a stress response. PMID:20844027

  3. IgE anti-respiratory syncytial virus antibodies detected in serum of pediatric patients with asthma.

    Science.gov (United States)

    Smith-Norowitz, Tamar A; Mandal, Mira; Joks, Rauno; Norowitz, Levana T; Weaver, Diana; Durkin, Helen G; Bluth, Martin H; Kohlhoff, Stephan

    2015-07-01

    Respiratory syncytial virus (RSV) causes lower respiratory tract disease in infants and young children, and is a public health concern, as is the increase in pediatric asthma. Respiratory viral infections may trigger asthma exacerbations. However, it remains unknown whether RSV infection may have a specific association with asthma. Total serum IgE, and IgE- and IgG-anti-RSV Ab responses were studied in older asthmatic compared with non-asthmatic children (M/F, mean age: 14) (N=30, N=43, respectively). We found: (1) total serum IgE was higher in asthmatic compared with non-asthmatics (Pasthma compared with no asthma (P=0.003; asthma (P=0.008), but not in asthma (P=0.64). Our findings indicate that IgE-anti-RSV Ab responses may play important roles in RSV infection and asthma.

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

    Directory of Open Access Journals (Sweden)

    Straliotto Selir M

    2001-01-01

    Full Text Available We analyzed the respiratory syncytial virus (RSV groups and their epidemiological pattern that were detected over the course of seven years in southern Brazil. The two RSV groups co-circulated each year, but frequencies of groups A and B varied both between and within yearly outbreaks. In 1991, group A predominated over group B (p=0.0016. RSV outbreaks analyzed showed a temperature-dependent pattern and no association with rainfall, similarly to other countries from southern South America. Knowledge of the variants is important in terms of both diagnosis and definition of a vaccine composition.

  5. Interferon γ expressed by a recombinant respiratory syncytial virus attenuates virus replication in mice without compromising immunogenicity

    OpenAIRE

    1999-01-01

    Interferon γ (IFN-γ) has pleiotropic biological effects, including intrinsic antiviral activity as well as stimulation and regulation of immune responses. An infectious recombinant human respiratory syncytial virus (rRSV/mIFN-γ) was constructed that encodes murine (m) IFN-γ as a separate gene inserted into the G-F intergenic region. Cultured cells infected with rRSV/mIFN-γ secreted 22 μg mIFN-γ per 106 cells. The replication of rRSV/mIFN-γ, but not that of a control chimeric rRSV containing t...

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

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    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

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

    Science.gov (United States)

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

    2016-07-01

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

  8. Bovine rhinitis viruses are common in U.S. cattle with bovine respiratory disease.

    Science.gov (United States)

    Hause, Ben M; Collin, Emily A; Anderson, Joe; Hesse, Richard A; Anderson, Gary

    2015-01-01

    Bovine rhinitis viruses (BRV) are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1) has been identified while bovine rhinitis A virus 2 (BRAV2) and bovine rhinitis B virus (BRBV) were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1) was also determined from a historical isolate to enable further molecular epidemiological studies. A 5'-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4%) were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations.

  9. Bovine rhinitis viruses are common in U.S. cattle with bovine respiratory disease.

    Directory of Open Access Journals (Sweden)

    Ben M Hause

    Full Text Available Bovine rhinitis viruses (BRV are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1 has been identified while bovine rhinitis A virus 2 (BRAV2 and bovine rhinitis B virus (BRBV were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1 was also determined from a historical isolate to enable further molecular epidemiological studies. A 5'-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4% were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations.

  10. 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.

  11. Immunogenicity and efficacy of alphavirus-derived replicon vaccines for respiratory syncytial virus and human metapneumovirus in nonhuman primates.

    Science.gov (United States)

    Bates, John T; Pickens, Jennifer A; Schuster, Jennifer E; Johnson, Monika; Tollefson, Sharon J; Williams, John V; Davis, Nancy L; Johnston, Robert E; Schultz-Darken, Nancy; Slaughter, James C; Smith-House, Frances; Crowe, James E

    2016-02-10

    Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development.

  12. Affinity-purified respiratory syncytial virus antibodies from intravenous immunoglobulin exert potent antibody-dependent cellular cytotoxicity.

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    Nimesh Gupta

    Full Text Available Mixed infections are one of the major therapeutic challenges, as the current strategies have had limited success. One of the most common and widespread conditions of mixed infection is respiratory syncytial virus-mediated pathology of the respiratory tract in children. There is a dire need for the development of novel therapeutic approaches during mixed infections. Therapeutic intravenous immunoglobulin preparations, obtained from plasma pools of healthy donors have been used in immune deficiencies. This study was thus designed to characterize the functional efficacy of RSV-specific antibodies in IVIg. To explore the functional ability of these affinity-purified RSV-specific antibodies, the antibody-dependent and complement dependent cytotoxicity was determined using peripheral cells of healthy donors. This study demonstrates the existence of highly potent RSV-specific antibodies in IVIg preparations and provides the basis for the use of IVIg as broad-spectrum protective shield to RSV-infected children during mixed infections.

  13. [Respiratory syncytial virus (RSV) infections in the pediatric teaching hospital Charles de Gaulle of Ouagadougou, Burkina Faso].

    Science.gov (United States)

    Ouédraogo Yugbaré, S O; Ouédraogo, R; Nenebi, A; Traoré, B; Congo, L; Yonli, F; Kima, D; Bonané, P; Yé, D; Plantier, J-C; Vabret, A; Marguet, C; Gueudin, M

    2016-02-01

    Human respiratory syncytial virus (RSV) infections are little known in Burkina Faso. The objective of our work is to study the epidemiological and clinical aspects of RSV infections in infants in the Pediatric Teaching Hospital Charles de Gaulle of Ouagadougou. Between July 1(st) 2010 and June 30(th) 2011, we analyzed by direct immunofluorescence and PCR nasopharyngeal swabs from children from 0 to 36 months old. All in all, 210 patients among whom 74 from the external consultation (35.2%) and 136 hospitalized (64.7%) benefited from a nasopharyngeal aspiration. The motives for consultation were cough (91.7%), rhinitis (79.2%), fever (79.2%) and respiratory distress syndrome (66.7%). The evoked diagnoses were predominantly the acute bronchiolitis in 14 cases (58.3%) followed by the acute pulmonary disease in 7 patients (26.2%) then flue in 1 patient (16.7%). We detected by direct immunofluorescence the antigens of the respiratory viruses in 21 nasopharyngeal aspirations with 10 cases of respiratory syncytial virus (RSV) infections (47.6%). The PCR realized on 208 samples allowed to identify 153 positive samples (73.2%) with 24 RSV, i.e. a global prevalence of 16.1% with a peak of 18 cases (75%). In October, all the patients benefited from an often multiple antibiotic treatment of at least 10 days which was not still necessary. The evolution was favorable for all patients. This study confirms the important place of the viruses which are detected in 70% of the cases. The PCR multiplex, certainly expensive but effective and successful, deserves to be used in our developing countries to avoid the irrational prescription of antibiotic.

  14. A peptide mimic of a protective epitope of respiratory syncytial virus selected from a combinatorial library induces virus-neutralizing antibodies and reduces viral load in vivo

    NARCIS (Netherlands)

    Chargelegue, D.; Obeid, O.E.; Hsu, S.C.; Shaw, M.D.; Denbury, A.N.; Taylor, G.; Steward, M.W.

    1998-01-01

    Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis and pneumonia in infants and young children worldwide. As yet, there is no effective vaccine against RSV infection, and previous attempts to develop a formalin-inactivated vaccine resulted in exacerbated disease in recipi

  15. Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Preterm Infants Without Chronic Lung Disease or Congenital Heart Disease

    NARCIS (Netherlands)

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

    2016-01-01

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

  16. Population based external validation of a European predictive model for respiratory syncytial virus hospitalization of premature infants born 33 to 35 weeks of gestational age

    DEFF Research Database (Denmark)

    Stensballe, Lone G; Fullarton, John R; Carbonell-Estrany, Xavier

    2010-01-01

    Prospectively collected population-based data on 2529 Danish infants born at 33 to 35 weeks of gestation were used to validate an European predictive model of respiratory syncytial virus (RSV) hospitalization. The model was found to be robust with a diagnostic accuracy of 65.9% to distinguish bet...

  17. Interleukin-27 inhibits vaccine-enhanced pulmonary disease following respiratory syncytial virus infection by regulating cellular memory responses.

    Science.gov (United States)

    Zeng, Ruihong; Zhang, Huixian; Hai, Yan; Cui, Yuxiu; Wei, Lin; Li, Na; Liu, Jianxun; Li, Caixia; Liu, Ying

    2012-04-01

    Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract disease in young children. In the 1960s, infants vaccinated with formalin-inactivated RSV developed a more severe disease characterized by excessive inflammatory immunopathology in lungs upon natural RSV infection. The fear of causing the vaccine-enhanced disease (VED) is an important obstacle for development of safe and effective RSV vaccines. The recombinant vaccine candidate G1F/M2 immunization also led to VED. It has been proved that cellular memory induced by RSV vaccines contributed to VED. Interleukin-27 (IL-27) and IL-23 regulate Th1, Th17, and/or Th2 cellular immune responses. In this study, mice coimmunized with pcDNA3-IL-27 and G1F/M2 were fully protected and, importantly, did not develop vaccine-enhanced inflammatory responses and immunopathology in lungs after RSV challenge, which was correlated with moderate Th1-, suppressed Th2-, and Th17-like memory responses activated by RSV. In contrast, G1F/M2- or pcDNA3-IL-23+G1F/M2-immunized mice, in which robust Th2- and Th17-like memory responses were induced, developed enhanced pulmonary inflammation and severe immunopathology. Mice coimmunized with G1F/M2 and the two cytokine plasmids exhibited mild inflammatory responses as well as remarkable Th1-, suppressed Th2-, and Th17-like memory responses. These results suggested that Th1-, Th2-, and Th17-like memory responses and, in particular, excessive Th2- and Th17-like memory responses were closely associated with VED; IL-27 may inhibit VED following respiratory syncytial virus infection by regulating cellular memory responses.

  18. Opposing Roles of Membrane and Soluble Forms of the Receptor for Advanced Glycation End Products in Primary Respiratory Syncytial Virus Infection

    OpenAIRE

    2012-01-01

    Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager−/− ) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflam...

  19. Application of Functional Genomics for Bovine Respiratory Disease Diagnostics.

    Science.gov (United States)

    Rai, Aswathy N; Epperson, William B; Nanduri, Bindu

    2015-01-01

    Bovine respiratory disease (BRD) is the most common economically important disease affecting cattle. For developing accurate diagnostics that can predict disease susceptibility/resistance and stratification, it is necessary to identify the molecular mechanisms that underlie BRD. To study the complex interactions among the bovine host and the multitude of viral and bacterial pathogens, as well as the environmental factors associated with BRD etiology, genome-scale high-throughput functional genomics methods such as microarrays, RNA-seq, and proteomics are helpful. In this review, we summarize the progress made in our understanding of BRD using functional genomics approaches. We also discuss some of the available bioinformatics resources for analyzing high-throughput data, in the context of biological pathways and molecular interactions. Although resources for studying host response to infection are avail-able, the corresponding information is lacking for majority of BRD pathogens, impeding progress in identifying diagnostic signatures for BRD using functional genomics approaches.

  20. Prevention of respiratory syncytial virus infections Prevenção das infecções pelo vírus sincicial respiratório

    Directory of Open Access Journals (Sweden)

    Lucia Ferro Bricks

    2001-06-01

    Full Text Available Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia, and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.Em todo o mundo, o vírus sincicial respiratório é o principal agente de infecções agudas das vias aéreas baixas em lactentes jovens e crianças. Aos dois anos de idade, praticamente todas as crianças já foram infectadas, e as reinfeções são comuns

  1. The effects of disodium cromoglycate on enhanced adherence of Haemophilus influenzae to A549 cells infected with respiratory syncytial virus.

    Science.gov (United States)

    Fukasawa, Chie; Ishiwada, Naruhiko; Ogita, Junko; Hishiki, Haruka; Kohno, Yoichi

    2009-08-01

    Nontypeable Haemophilus influenzae (NTHi) secondary infection often complicates respiratory syncytial virus (RSV) infections. Previous studies have revealed that RSV infections enhance NTHi adherence to airway epithelial cells. In this study, we investigated the effects of disodium cromoglycate (DSCG) and corticosteroids, which are frequently used for the treatment of wheezing often related to RSV infections, on the adherence of NTHi to RSV-infected A549 cells. DSCG inhibited enhanced adherence of NTHi to RSV-infected A549 cells, whereas dexamethasone (Dex) and fluticasone propionate (Fp) did not. DSCG suppressed the expression of ICAM-1, which is one of the NTHi receptors. Furthermore, DSCG exhibited an inhibitory effect on RSV infections. It is suggested that DSCG exerts an anti-RSV effect, and consequently attenuates the expression of NTHi receptors.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wathen, M.W.; Aeed, P.A.; Elhammer, A.P. (Upjohn Co., Kalamazoo, MI (United States))

    1991-03-19

    The oligosaccharide structures added to a chimeric protein (FG) composed of the extracellular domains of respiratory syncytial virus F and G proteins, expressed in the insect cell line Sf9, were investigated. Cells were labeled in vivo with ({sup 3}H)glucosamine and infected wit a recombinant baculovirus containing the FG gene. The secreted chimeric protein was isolated by immunoprecipitation and subjected to oligosaccharide analysis. The FG protein contains two types of O-linked oligosaccharides: GalNAc and Gal{beta}1-3GalNAc constituting 17 and 66% of the total number of structures respectively. Only one type of N-linked oligosaccharide, constituting the remaining 17% of the structures on FG, was detected: a trimannosyl core structure with a fucose residue linked {alpha}1-6 to the asparagine-linked N-acetylglucosamine.

  3. Evaluation of recent New Vaccine Surveillance Network data regarding respiratory syncytial virus hospitalization rates in US preterm infants.

    Science.gov (United States)

    DeVincenzo, John P; Ambrose, Christopher S; Makari, Doris; Weiner, Leonard B

    2016-04-01

    In July 2014, the Committee on Infectious Diseases (COID) updated their guidance on the use of palivizumab, recommending against use in preterm infants 29 to 35 weeks' gestational age (wGA). A primary data source cited to support this significant change was the low respiratory syncytial virus (RSV) hospitalization rate observed in the subpopulation of preterm (preterm infant data from the NVSN in the context of data regarding the use of palivizumab in this same time period. Data from the NVSN, an analysis of Florida Medicaid data, and a national survey of US in-hospital palivizumab administration demonstrated that during 2001 to 2007, palivizumab was administered to 59% to 83% of preterm infants born at preterm infants (preterm infant subgroups were evaluated as a function of chronologic age, preterm infants preterm infants given the small size of the analyzed subpopulation and the high use of palivizumab during the study period.

  4. Control methods for bovine respiratory disease for feedlot cattle.

    Science.gov (United States)

    Edwards, T A

    2010-07-01

    Vaccines and antibiotics are still relied upon as the standard methods of bovine respiratory disease (BRD) prevention, control, and therapy. Success in building disease resistance begins with genetic selection and continues with colostrum management and reducing pathogen exposure. Purchasing single-source cattle with a history of pre- and post-weaning procedures will minimize pathogen exposure and enhance immunity. Using cattle-handling techniques and facilities that promote low stress will allow host immune defenses to remain effective against bacterial and viral colonization. Lastly, controlling BRD must be managed through a comprehensive herd health immunization and management program that effectively addresses disease challenges common to the operation.

  5. Autocrine regulation of pulmonary inflammation by effector T-cell derived IL-10 during infection with respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Jie Sun

    2011-08-01

    Full Text Available Respiratory syncytial virus (RSV infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection.

  6. A Network Flow Approach to Predict Protein Targets and Flavonoid Backbones to Treat Respiratory Syncytial Virus Infection

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    José Eduardo Vargas

    2015-01-01

    Full Text Available Background. Respiratory syncytial virus (RSV infection is the major cause of respiratory disease in lower respiratory tract in infants and young children. Attempts to develop effective vaccines or pharmacological treatments to inhibit RSV infection without undesired effects on human health have been unsuccessful. However, RSV infection has been reported to be affected by flavonoids. The mechanisms underlying viral inhibition induced by these compounds are largely unknown, making the development of new drugs difficult. Methods. To understand the mechanisms induced by flavonoids to inhibit RSV infection, a systems pharmacology-based study was performed using microarray data from primary culture of human bronchial cells infected by RSV, together with compound-proteomic interaction data available for Homo sapiens. Results. After an initial evaluation of 26 flavonoids, 5 compounds (resveratrol, quercetin, myricetin, apigenin, and tricetin were identified through topological analysis of a major chemical-protein (CP and protein-protein interacting (PPI network. In a nonclustered form, these flavonoids regulate directly the activity of two protein bottlenecks involved in inflammation and apoptosis. Conclusions. Our findings may potentially help uncovering mechanisms of action of early RSV infection and provide chemical backbones and their protein targets in the difficult quest to develop new effective drugs.

  7. Inhibition of G1P3 expression found in the differential display study on respiratory syncytial virus infection

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    Li Lei

    2008-10-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the leading viral pathogen associated with bronchiolitis and lower respiratory tract disease in infants and young children worldwide. The respiratory epithelium is the primary initiator of pulmonary inflammation in RSV infections, which cause significant perturbations of global gene expression controlling multiple cellular processes. In this study, differential display reverse transcription polymerase chain reaction amplification was performed to examine mRNA expression in a human alveolar cell line (SPC-A1 infected with RSV. Results Of the 2,500 interpretable bands on denaturing polyacrylamide gels, 40 (1.6% cDNA bands were differentially regulated by RSV, in which 28 (70% appeared to be upregulated and another 12 (30% appeared to be downregulated. Forty of the expressed sequence tags (EST were isolated, and 20 matched homologs in GenBank. RSV infection upregulated the mRNA expression of chemokines CC and CXC and interfered with type α/β interferon-inducible gene expression by upregulation of MG11 and downregulation of G1P3. Conclusion RSV replication could induce widespread changes in gene expression including both positive and negative regulation and play a different role in the down-regulation of IFN-α and up-regulation of IFN-γ inducible gene expression, which suggests that RSV interferes with the innate antiviral response of epithelial cells by multiple mechanisms.

  8. Protective efficacy and immunogenicity of a combinatory DNA vaccine against Influenza A Virus and the Respiratory Syncytial Virus.

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    Viktoria Stab

    Full Text Available The Respiratory Syncytial Virus (RSV and Influenza A Virus (IAV are both two major causative agents of severe respiratory tract infections in humans leading to hospitalization and thousands of deaths each year. In this study, we evaluated the immunogenicity and efficacy of a combinatory DNA vaccine in comparison to the single component vaccines against both diseases in a mouse model. Intramuscular electroporation with plasmids expressing the hemagglutinin (HA of IAV and the F protein of RSV induced strong humoral immune responses regardless if they were delivered in combination or alone. In consequence, high neutralizing antibody titers were detected, which conferred protection against a lethal challenge with IAV. Furthermore, the viral load in the lungs after a RSV infection could be dramatically reduced in vaccinated mice. Concurrently, substantial amounts of antigen-specific, polyfunctional CD8⁺ T-cells were measured after vaccination. Interestingly, the cellular response to the hemagglutinin was significantly reduced in the presence of the RSV-F encoding plasmid, but not vice versa. Although these results indicate a suppressive effect of the RSV-F protein, the protective efficacy of the combinatory vaccine was comparable to the efficacy of both single-component vaccines. In conclusion, the novel combinatory vaccine against RSV and IAV may have great potential to reduce the rate of severe respiratory tract infections in humans without increasing the number of necessary vaccinations.

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

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    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.

  10. Non-typeable Haemophilus influenzae protects human airway epithelial cells from a subsequent respiratory syncytial virus challenge.

    Science.gov (United States)

    Hartwig, Stacey M; Ketterer, Margaret; Apicella, Michael A; Varga, Steven M

    2016-11-01

    Respiratory syncytial virus (RSV) and the common commensal and opportunistic pathogen, non-typeable Haemophilus influenzae (NTHi) both serve as a frequent cause of respiratory infection in children. Although it is well established that some respiratory viruses can increase host susceptibility to secondary bacterial infections, few studies have examined how commensal bacteria could influence a secondary viral response. Here, we examined the impact of NTHi exposure on a subsequent RSV infection of human bronchial epithelial cells (16HBE14o-). Co-culture of 16HBE14o- cells with NTHi resulted in inhibition of viral gene expression following RSV infection. 16HBE14o- cells co-cultured with heat-killed NTHi failed to protect against an RSV infection, indicating that protection requires live bacteria. However, NTHi did not inhibit influenza A virus replication, indicating that NTHi-mediated protection was RSV-specific. Our data demonstrates that prior exposure to a commensal bacterium such as NTHi can elicit protection against a subsequent RSV infection.

  11. Bovine coronavirus antibody titers at weaning negatively correlate with incidence of bovine respiratory disease in the feed yard

    Science.gov (United States)

    Bovine respiratory disease complex (BRDC) is a multifactorial disease caused by complex interactions among viral and bacterial pathogens, stressful management practices and host genetic variability. Although vaccines and antibiotic treatments are readily available to prevent and treat infection caus...

  12. Short communication. Prevalence of antibodies against Parainfluenza virus type 3, Respiratory syncitial virus and bovine Herpesvirus type 1 in sheep from Northern Prefectures of Japan

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    Massimo Giangaspero

    2013-09-01

    Full Text Available Ovine sera collected in the Prefectures of Hokkaido, Aomori and Iwate in the Northern Japan were examined for the presence of antibodies against Respiratory syncytial virus (RSV, bovine Herpesvirus type 1 (infectious bovine rhinotracheitis: IBR and Parainfluenza virus type 3 (PIV3 using serum neutralisation (SN and enzyme-linked immunosorbent assay (ELISA tests. Twenty-three animals (11.73% out of the 196 tested were sero-positive to PIV3. Sixteen animals (8.69% out of the 184 tested reacted to RSV. No animals were positive to IBR antigen. Sero-conversions to PIV3 were detected in Hokkaido and Iwate (14.92% and 8.82%, respectively. Antibodies against RSV were detected in Hokkaido (9.23% and Aomori (14.28%. Although no diagnostic measures were in place, the infections did not appear to be related to any reduction in sheep productivity.

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

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    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.

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

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    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.

  15. 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.

  16. The preventive effect of vaccine prophylaxis on severe respiratory syncytial virus infection:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Tongna; Zhu; Chuanlong; Zhang; Li; Yu; Jingxian; Chen; Huan; Qiu; Weiwei; Lyu; Shenghai; Huang

    2015-01-01

    Respiratory syncytial virus(RSV) is the key underlying cause of acute lower respiratory tract infection in infants; however, no licensed vaccine against RSV infection is currently available. This study was undertaken to assess the preventive effect of vaccine on RSV infection. In this metaanalysis, 1,792 published randomized clinical trials of RSV vaccines from Jan 1973 to Sep 2015 were examined. Among thirteen studies that met the inclusion criteria, eleven studies estimated the impact of RSV vaccines and four studies estimated the effect of adjuvants. The odds ratios(ORs) were 0.31(95% CI, 0.15–0.67) and 0.62(95% CI, 0.29–1.34), respectively. We found that RSV subunit vaccines can significantly reduce the incidence of RSV infection and that whether vaccination with adjuvant therapy was an effective strategy still remained to be studied. This analysis of the preventive effect of vaccines on RSV infection has direct applications for the prevention of RSV infections.

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

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    Lamarão Letícia

    2012-05-01

    Full Text Available Abstract Background Childhood pneumonia and bronchiolitis is a leading cause of illness and death in young children worldwide with Respiratory Syncytial Virus (RSV as the main viral cause. RSV has been associated with annual respiratory disease outbreaks and bacterial co-infection has also been reported. This study is the first RSV epidemiological study in young children hospitalized with community-acquired pneumonia (CAP in Belém city, Pará (Northern Brazil. Methods With the objective of determining the prevalence of RSV infection and evaluating the patients’ clinical and epidemiological features, we conducted a prospective study across eight hospitals from November 2006 to October 2007. In this study, 1,050 nasopharyngeal aspirate samples were obtained from hospitalized children up to the age of three years with CAP, and tested for RSV antigen by direct immunofluorescence assay and by Reverse Transcription Polymerase Chain Reaction (RT-PCR for RSV Group identification. Results RSV infection was detected in 243 (23.1% children. The mean age of the RSV-positive group was lower than the RSV-negative group (12.1 months vs 15.5 months, pppppp Conclusion The present study highlights the relevance of RSV infection in hospitalized cases of CAP in our region; our findings warrant the conduct of further investigations which can help design strategies for controlling the disease.

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

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    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.

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

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    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.

  20. 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

  1. 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.

  2. 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 viru

  3. Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine.

    Science.gov (United States)

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

    2012-01-01

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

  4. Genetic variation of human respiratory syncytial virus among children with fever and respiratory symptoms in Shanghai, China, from 2009 to 2012.

    Science.gov (United States)

    Liu, Jia; Mu, Yonglin; Dong, Wei; Yao, Fujia; Wang, Lili; Yan, Huajie; Lan, Ke; Zhang, Chiyu

    2014-10-01

    Human respiratory syncytial virus (HRSV) of genus Pneumovirus is one of the most common pathogens causing severe acute lower respiratory tract infection in infants and children. No information on the genotype distribution of HRSV is available in East China (e.g. Shanghai). From August 2009 to December 2012, 2407 nasopharyngeal swabs were collected from outpatient children with fever and respiratory symptoms in Shanghai. HRSV infection was determined using a multiplex RT-PCR assay. The second hypervariable region (HVR2) of G protein gene of HRSV was amplified and sequenced from HRSV positive samples. Genotypes were characterized by phylogenetic analyses. Of 2407 nasopharyngeal samples, 184 (7.6%) were tested as HRSV positive. From 160 positive subjects with sufficient nasopharyngeal samples, 69 HVR2 sequences were obtained by RT-PCR and sequencing. Three HRSV epidemic seasons were observed from August 2009 to December 2012, and an extreme outbreak of HRSV occurred in the 2009-2010 epidemic season. A genotype shift of predominant HRSV strains from B group in the 2009-2010 epidemic season to group A in the subsequent epidemic seasons was observed. Ten HRSV genotypes, including four group A genotypes NA1, NA3, NA4, and ON1, and six group B genotypes BA9, BA10, SAB4, CB1, BAc, and BA?, were detected in Shanghai. Seven genotypes (NA1, BA9-10, SAB4, CB1, BAc and BA?) were found in the 2009-2010 epidemic season. The co-circulation of multiple genotypes was associated with the extreme outbreak of HRSV among children with fever and respiratory symptoms in the 2009-2010 epidemic season.

  5. A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life

    DEFF Research Database (Denmark)

    Linstow, Michael Ernst Von; Hogh, M.; Nordbo, S.A.;

    2008-01-01

    Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are important respiratory pathogens with similar symptomatology. The aim of this prospective birth cohort study was to identify risk factors for an hMPV or RSV infection during the first year of life in unselected healthy children......% CI:0.09-0.85). Risk factors for RSV hospitalisation (n = 11) were: (1) older siblings (OR = 4.49; 95% CI: 1.08-18.73) and (2) smoking in the household (OR = 5.06; 95% CI: 1.36-18.76). Exclusive breastfeeding for the first 14 days of life protected against hospitalisation (OR = 0.21; 95% CI:0...

  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

    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 ...

  7. The bovine paranasal sinuses: Bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens

    Science.gov (United States)

    O’Neill, Rónan G.; Lee, Alison M.; McElroy, Máire C.; More, Simon J.; Monagle, Aisling; Earley, Bernadette; Cassidy, Joseph P.

    2017-01-01

    The bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99) and of cattle submitted for post-mortem examination (PME: n = 34) were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (BPIV-3). Overall, the paranasal sinuses were either predominantly sterile or did not contain detectable microbes (83.5%: 94.9% of clinically normal and 50.0% of cattle submitted for PME). Bacteria, including BRD causing pathogens, were identified in relatively small numbers of cattle (<10%). While serology indicated widespread exposure of both clinically normal and cattle submitted for PME to BPIV-3 and BRSV (seroprevalences of 91.6% and 84.7%, respectively), PCR identified BPIV-3 in only one animal. To further explore these findings we investigated the potential role of the antimicrobial molecule nitric oxide (NO) within paranasal sinus epithelium using immunohistochemistry. Expression of the enzyme responsible for NO synthesis, inducible nitric oxide synthase (iNOS), was detected to varying degrees in 76.5% of a sub-sample of animals suggesting production of this compound plays a similar protective role in the bovine sinus as it does in humans. PMID:28282443

  8. Vaccination against respiratory syncytial virus in pregnancy: a suitable tool to combat global infant morbidity and mortality?

    Science.gov (United States)

    Saso, Anja; Kampmann, Beate

    2016-08-01

    Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia in early childhood (ie, younger than 2 years), responsible for high infant morbidity and mortality worldwide. It is widely accepted that an effective vaccine against RSV would have a major impact on child health globally. Despite the setbacks of the clinical trials in the 1960s, there has been a recent and significant revival of interest in vaccines against RSV, with several promising candidates undergoing evaluation. In this Review, we describe the epidemiological and immunological background to RSV infection and subsequently focus on the promising pipeline of RSV vaccine development. We discuss the potential for implementation of a safe and immunogenic RSV vaccine within the context of global health and with regards to a range of strategies, including vaccination of women during pregnancy, which is likely to emerge as a beneficial and feasible public health tool. This approach would provide interim protection to vulnerable, RSV-naive infants and other high risk groups, in which the burden of admission to hospital and death is greatest. Extending research and implementation from resource-rich to resource-poor settings is required to enhance our understanding of RSV immunity and inform vaccine development and delivery strategies for all settings. We summarise key outstanding issues for researchers and policy makers to understand the interplay of biological and non-biological factors affecting design and distribution of a successful RSV vaccine globally.

  9. A Numerically Subdominant CD8 T Cell Response to Matrix Protein of Respiratory Syncytial Virus Controls Infection with Limited Immunopathology.

    Directory of Open Access Journals (Sweden)

    Jie Liu

    2016-03-01

    Full Text Available CD8 T cells are involved in pathogen clearance and infection-induced pathology in respiratory syncytial virus (RSV infection. Studying bulk responses masks the contribution of individual CD8 T cell subsets to protective immunity and immunopathology. In particular, the roles of subdominant responses that are potentially beneficial to the host are rarely appreciated when the focus is on magnitude instead of quality of response. Here, by evaluating CD8 T cell responses in CB6F1 hybrid mice, in which multiple epitopes are recognized, we found that a numerically subdominant CD8 T cell response against DbM187 epitope of the virus matrix protein expressed high avidity TCR and enhanced signaling pathways associated with CD8 T cell effector functions. Each DbM187 T effector cell lysed more infected targets on a per cell basis than the numerically dominant KdM282 T cells, and controlled virus replication more efficiently with less pulmonary inflammation and illness than the previously well-characterized KdM282 T cell response. Our data suggest that the clinical outcome of viral infections is determined by the integrated functional properties of a variety of responding CD8 T cells, and that the highest magnitude response may not necessarily be the best in terms of benefit to the host. Understanding how to induce highly efficient and functional T cells would inform strategies for designing vaccines intended to provide T cell-mediated immunity.

  10. Structure of a Major Antigenic Site on the Respiratory Syncytial Virus Fusion Glycoprotein in Complex with Neutralizing Antibody 101F

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-11-19

    Respiratory syncytial virus (RSV) is a major cause of pneumonia and bronchiolitis in infants and elderly people. Currently there is no effective vaccine against RSV, but passive prophylaxis with neutralizing antibodies reduces hospitalizations. To investigate the mechanism of antibody-mediated RSV neutralization, we undertook structure-function studies of monoclonal antibody 101F, which binds a linear epitope in the RSV fusion glycoprotein. Crystal structures of the 101F antigen-binding fragment in complex with peptides from the fusion glycoprotein defined both the extent of the linear epitope and the interactions of residues that are mutated in antibody escape variants. The structure allowed for modeling of 101F in complex with trimers of the fusion glycoprotein, and the resulting models suggested that 101F may contact additional surfaces located outside the linear epitope. This hypothesis was supported by surface plasmon resonance experiments that demonstrated 101F bound the peptide epitope {approx}16,000-fold more weakly than the fusion glycoprotein. The modeling also showed no substantial clashes between 101F and the fusion glycoprotein in either the pre- or postfusion state, and cell-based assays indicated that 101F neutralization was not associated with blocking virus attachment. Collectively, these results provide a structural basis for RSV neutralization by antibodies that target a major antigenic site on the fusion glycoprotein.

  11. A respiratory syncytial virus replicon that is noncytotoxic and capable of long-term foreign gene expression.

    Science.gov (United States)

    Malykhina, Olga; Yednak, Mark A; Collins, Peter L; Olivo, Paul D; Peeples, Mark E

    2011-05-01

    Respiratory syncytial virus (RSV) infection of most cultured cell lines causes cell-cell fusion and death. Cell fusion is caused by the fusion (F) glycoprotein and is clearly cytopathic, but other aspects of RSV infection may also contribute to cytopathology. To investigate this possibility, we generated an RSV replicon that lacks all three of its glycoprotein genes and so cannot cause cell-cell fusion or virus spread. This replicon includes a green fluorescent protein gene and an antibiotic resistance gene to enable detection and selection of replicon-containing cells. Adaptive mutations in the RSV replicon were not required for replicon maintenance. Cells containing the replicon could be cloned and passaged many times in the absence of antibiotic selection, with 99% or more of the cells retaining the replicon after each cell division. Transient expression of the F and G (attachment) glycoproteins supported the production of virions that could transfer the replicon into most cell lines tested. Since the RSV replicon is not toxic to these cultured cells and does not affect their rate of cell division, none of the 8 internal viral proteins, the viral RNA transcripts, or the host response to these molecules or their activities is cytopathic. However, the level of replicon genome and gene expression is controlled in some manner well below that of complete virus and, as such, might avoid cytotoxicity. RSV replicons could be useful for cytoplasmic gene expression in vitro and in vivo and for screening for compounds active against the viral polymerase.

  12. Contribution of cysteine residues in the extracellular domain of the F protein of human respiratory syncytial virus to its function

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    Melero José A

    2006-05-01

    Full Text Available Abstract The mature F protein of all known isolates of human respiratory syncytial virus (HRSV contains fifteen absolutely conserved cysteine (C residues that are highly conserved among the F proteins of other pneumoviruses as well as the paramyxoviruses. To explore the contribution of the cysteines in the extracellular domain to the fusion activity of HRSV F protein, each cysteine was changed to serine. Mutation of cysteines 37, 313, 322, 333, 343, 358, 367, 393, 416, and 439 abolished or greatly reduced cell surface expression suggesting these residues are critical for proper protein folding and transport to the cell surface. As expected, the fusion activity of these mutations was greatly reduced or abolished. Mutation of cysteine residues 212, 382, and 422 had little to no effect upon cell surface expression or fusion activity at 32°C, 37°C, or 39.5°C. Mutation of C37 and C69 in the F2 subunit either abolished or reduced cell surface expression by 75% respectively. None of the mutations displayed a temperature sensitive phenotype.

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

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, Kurt A.; Settembre, Ethan C.; Shaw, Christine A.; Dey, Antu K.; Rappuoli, Rino; Mandl, Christian W.; Dormitzer, Philip R.; Carfi, Andrea (Novartis)

    2012-02-07

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

  14. Residues in human respiratory syncytial virus P protein that are essential for its activity on RNA viral synthesis.

    Science.gov (United States)

    Asenjo, Ana; Mendieta, Jesús; Gómez-Puertas, Paulino; Villanueva, Nieves

    2008-03-01

    Human respiratory syncytial virus (HRSV) P protein, 241 amino acid long, is a structural homotetrameric phosphoprotein. Viral transcription and replication processes are dependent on functional P protein interactions inside viral ribonucleoprotein complexes (RNPs). Binding capacity to RNPs proteins and transcription and replication complementation analyses, using inactive P protein variants, have identified residues essential for functional interactions with itself, L, N and M2-1 proteins. P protein may establish some of these interactions as monomer, but efficient viral transcription and replication requires P protein oligomerization through the central region of the molecule. A structurally stable three-dimensional model has been generated in silico for this region (residues 98-158). Our analysis has indicated that P protein residues L135, D139, E140 and L142 are involved in homotetramerization. Additionally, the residues D136, S156, T160 and E179 appear to be essential for P protein activity on viral RNA synthesis and very high turnover phosphorylation at S143, T160 and T210 could regulate it. Thus, compounds targeted to those of these residues, located in the modeled three-dimensional structure, could have specific anti-HRSV effect.

  15. 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.

  16. Kinetics of antibody-induced modulation of respiratory syncytial virus antigens in a human epithelial cell line

    Directory of Open Access Journals (Sweden)

    Gómez-Garcia Beatriz

    2007-07-01

    Full Text Available Abstract Background The binding of viral-specific antibodies to cell-surface antigens usually results in down modulation of the antigen through redistribution of antigens into patches that subsequently may be internalized by endocytosis or may form caps that can be expelled to the extracellular space. Here, by use of confocal-laser-scanning microscopy we investigated the kinetics of the modulation of respiratory syncytial virus (RSV antigen by RSV-specific IgG. RSV-infected human epithelial cells (HEp-2 were incubated with anti-RSV polyclonal IgG and, at various incubation times, the RSV-cell-surface-antigen-antibody complexes (RSV Ag-Abs and intracellular viral proteins were detected by indirect immunoflourescence. Results Interaction of anti-RSV polyclonal IgG with RSV HEp-2 infected cells induced relocalization and aggregation of viral glycoproteins in the plasma membrane formed patches that subsequently produced caps or were internalized through clathrin-mediated endocytosis participation. Moreover, the concentration of cell surface RSV Ag-Abs and intracellular viral proteins showed a time dependent cyclic variation and that anti-RSV IgG protected HEp-2 cells from viral-induced death. Conclusion The results from this study indicate that interaction between RSV cell surface proteins and specific viral antibodies alter the expression of viral antigens expressed on the cells surface and intracellular viral proteins; furthermore, interfere with viral induced destruction of the cell.

  17. Estimation of nasal shedding and seroprevalence of organisms known to be associated with bovine respiratory disease in Australian live export cattle.

    Science.gov (United States)

    Moore, S Jo; O'Dea, Mark A; Perkins, Nigel; O'Hara, Amanda J

    2015-01-01

    The prevalence of organisms known to be associated with bovine respiratory disease (BRD) was investigated in cattle prior to export. A quantitative reverse transcription polymerase chain reaction assay was used to detect nucleic acids from the following viruses and bacteria in nasal swab samples: Bovine coronavirus (BoCV; Betacoronavirus 1), Bovine herpesvirus 1 (BoHV-1), Bovine viral diarrhea virus 1 (BVDV-1), Bovine respiratory syncytial virus (BRSV), Bovine parainfluenza virus 3 (BPIV-3), Histophilus somni, Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida. Between 2010 and 2012, nasal swabs were collected from 1,484 apparently healthy cattle destined for export to the Middle East and Russian Federation. In addition, whole blood samples from 334 animals were tested for antibodies to BoHV-1, BRSV, BVDV-1, and BPIV-3 using enzyme-linked immunosorbent assay. The nasal prevalence of BoCV at the individual animal level was 40.1%. The nasal and seroprevalence of BoHV-1, BRSV, BVDV-1, and BPIV-3 was 1.0% and 39%, 1.2% and 46%, 3.0% and 56%, and 1.4% and 87%, respectively. The nasal prevalence of H. somni, M. bovis, M. haemolytica, and P. multocida was 42%, 4.8%, 13.4%, and 26%, respectively. Significant differences in nasal and seroprevalence were detected between groups of animals from different geographical locations. The results of the current study provide baseline data on the prevalence of organisms associated with BRD in Australian live export cattle in the preassembly period. This data could be used to develop strategies for BRD prevention and control prior to loading.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    (RSV) bronchiolitic respiratory symptoms. OBJECTIVES: To evaluate the efficacy and safety of montelukast, 4 and 8 mg, in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large, multicenter study. METHODS: This was a double-blind study of 3- to 24-month-old children who...... had been hospitalized for a first or second episode of physician-diagnosed RSV bronchiolitis and who tested positive for RSV. Patients (n = 979) were randomized to placebo or to montelukast at 4 or 8 mg/day for 4 weeks (period I) and 20 weeks (period II). The primary end point was percentage symptom.......7 (0.0, 11.3) for montelukast (4 mg) minus placebo and 5.9 (0.1, 11.7) for montelukast (8 mg) minus placebo. CONCLUSIONS: In this study, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children....

  19. Palivizumab prophylaxis of respiratory syncytial virus disease in 2000-2001: results from The Palivizumab Outcomes Registry.

    Science.gov (United States)

    Parnes, Curt; Guillermin, Judith; Habersang, Rolf; Nicholes, Peggy; Chawla, Vijay; Kelly, Tammy; Fishbein, Judith; McRae, Patty; Goessler, Mary; Gatti, Antoinette; Calcagno, John A; Eki, Cheryl; Harris, Kristen A; Joyave, Joseph; McFarland, Kathy; Protter, Paul; Sullivan, Mary; Stanford, Allan; Lovett, Nancy; Ortiz, Marisol; Rojas, Sharon; Cyrus, Scott; Cyrus, Janell; Cohen, Stuart; Buchin, Debbie; Riordan, Linda; Zuniga, Monica; Shah, Rupa; Minard, Carmen; Quintin, Arden; Douglas, Glenda; van Houten, John; Freutner, Sharyn; Chartrand, Stephen; Nowatzke, Patsy; Romero, Jose; Rhodes, Torunn; Benoit, Michelle; Walter, Emmanuel; Walker, Leslie; DeBonnett, Laurie; Cross, Mia; Free, Teresa; Martin, Sharman; Shank, Karen; Guedes, Ben; Atkinson, Lee Ann; Halpin, George J; Rouse, Kathy; Hand, Ivan; Geiss, Donna; Marshall, James R; Burleson, Lois; Boland, Jim; Seybold, Kelsey; Hunter, Vicki; Unfer, Susan; Schmucker, Jackie; Gley, Margaret; Marcus, Michael; Thompson, Patricia; Milla, Paulino; Young, Connie; Zanni, Robert; Zinno, Virginia; Fetter-Zarzeka, Alexandra; Busey, Amanda; Sokunbi, Modupe A; Airington, Sherrie; Richard, Nancy; Muraligopal, Vellore; Lewis, Stephanie; Weber, F Thomas; Giordano, Beverly P; Linehan, Denise; Roach, Jane; Davis, Randle; Rzepka, Andrew A; Booth, Teri; Smeltzer, David; Walsh, Jeanne; Arispe, Emilio; Rowley, Rhonda; Bolling, Christopher; Botts, Tanya; Haskett, Kateri; Raby, Deana; Batiz, Evelyn; Gelfand, Andrew; Farrell, Lynn; Butler, Stephen; Colby, Linda; Schochet, Peter; Bentler, Julie; Hirsch, David; Wilkinson, Lisa; Aaronson, Allen; Bennett, Eleanora; Wingate, Julie; Quinn, Dawn; Komendowski, Katherine; Deckard, Marcia; Frogel, Michael; Nerwen, Cliff; Copenhaver, Steven; Prater, Michele; Wolsztein, Jacob; Mackey, Kristine; Benbow, Marshall; Naranjo, Marisela; Hensley, Sandra; Hayes, Cindy; Sadeghi, Hossein; Lawson, Sally May; McCall, Mark; Combs, Karla; Ledbetter, Joel; Sarnosky, Karen; Swafford, Cathy; Speer, Michael; Barton, Wendy J; Mink, J W; Lemm, Dianne; Hudak, Mark; Case, Elizabeth; Rowen, Judith; Fuentes, Sandra; Pane, Carly; Richardson, Leslie; Chavarria, Cesar; Cassino, Deanne; Ghaffari, Kourosh; Carroll, Carol; Lee, Haesoon; Guclu, Lydia; Johnson, Christopher; Blum, Valerie; Boron, Marnie L; Sorrentino, Mark; Hirsch, Robert L; Van Veldhuisen, Paul C; Smith, Carol

    2003-06-01

    The objective of the Registry was to characterize the population of infants receiving prophylaxis for respiratory syncytial virus (RSV) disease by describing the patterns and scope of usage of palivizumab in a cross section of US infants. RSV hospitalization outcomes were also described. The Palivizumab (Synagis, MedImmune, Inc., 25 West Watkins Mill Road, Gaithersburg, MD 20878) Outcomes Registry was a prospective multicenter survey conducted at 63 sites. Demographics, injection history, and RSV hospitalization outcomes were collected on 2,116 infants receiving palivizumab. Infants were enrolled in the Registry between September 1, 2000-March 1, 2001, at the time of their first injection. Infants born at less than 32 weeks of gestation accounted for 47% of infants enrolled, and those between 32-35 weeks accounted for 45%; approximately 8% were greater than 35 weeks of gestation. Lower RSV hospitalization rates were observed in infants who had greater adherence to regularly scheduled injections. Nearly one-half of all hospitalizations occurred within the first and second injection intervals, suggesting the importance of early RSV protection. The confirmed RSV hospitalization rate of all infants in the Registry was 2.9%; the rate was 5.8% in infants with chronic lung disease of infancy, and 2.1% in premature infants without chronic lung disease. In conclusion, these data support the continued effectiveness of palivizumab prophylaxis for severe RSV lower respiratory tract disease in a large cohort of high-risk infants from geographically diverse pediatric offices and clinics. The Palivizumab Outcomes Registry provides an opportunity to assess palivizumab utilization and clinical effectiveness in the US.

  20. Genetic diversity in the G protein gene of group A human respiratory syncytial viruses circulating in Riyadh, Saudi Arabia.

    Science.gov (United States)

    Almajhdi, Fahad N; Farrag, Mohamed A; Amer, Haitham M

    2014-01-01

    Human respiratory syncytial virus (HRSV) is a frequent cause of hospitalization and mortality in children worldwide. The molecular epidemiology and circulation pattern of HRSV in Saudi Arabia is mostly uncharted. In the current study, the genetic variability and phylogenetic relationships of HRSV type A strains circulating in Riyadh Province were explored. Nasopharyngeal aspirates were collected from hospitalized children with acute respiratory symptoms during the winter-spring seasons of 2007/08 and 2008/09. Among 175 samples analyzed, 39 (22.3 %) were positive for HRSV by one-step RT-PCR (59 % type A and 41 % type B). Propagation of positive samples in HEp-2 cells permitted the recovery of the first Saudi HRSV isolates. Genetic variability among Saudi HRSV-A strains was evaluated by sequence analysis of the complete attachment (G) protein gene. The nucleotide sequence was compared to representatives of the previously identified HRSV-A genotypes. Sequence and phylogenetic analysis showed that the strains examined in this study were very closely related at both the nucleotide and amino acid level, and all of them are clustered in the GA2 genotype (and mostly belonged to the NA-1 subtype). A total of 23 mutation sites, 14 of which resulted in an amino acid change, were recorded only in Saudi strains. This is the first report on genetic diversity of HRSV-A strains in Saudi Arabia. Further analysis of strains on a geographical and temporal basis is needed to fully understand HRSV-A circulation patterns in Saudi Arabia.

  1. Comparing Human Metapneumovirus and Respiratory Syncytial Virus: Viral Co-Detections, Genotypes and Risk Factors for Severe Disease

    Science.gov (United States)

    Moe, Nina; Krokstad, Sidsel; Stenseng, Inger Heimdal; Christensen, Andreas; Skanke, Lars Høsøien; Risnes, Kari Ravndal; Nordbø, Svein Arne; Døllner, Henrik

    2017-01-01

    Background It is unclarified as to whether viral co-detection and human metapneumovirus (HMPV) genotypes relate to clinical manifestations in children with HMPV and lower respiratory tract infection (LRTI), and if the clinical course and risk factors for severe LRTI differ between HMPV and respiratory syncytial virus (RSV). Methods We prospectively enrolled hospitalized children aged <16 years with LRTI from 2006 to 2015. Children were clinically examined, and nasopharyngeal aspirates were analyzed using semi-quantitative, real-time polymerase chain reaction tests for HMPV, RSV and 17 other pathogens. HMPV-positive samples were genotyped. Results A total of 171 children had HMPV infection. HMPV-infected children with single virus (n = 106) and co-detections (n = 65) had similar clinical manifestations. No clinical differences were found between HMPV genotypes A (n = 67) and B (n = 80). The HMPV-infected children were older (median 17.2 months) than RSV-infected children (median 7.3 months, n = 859). Among single virus-infected children, no differences in age-adjusted LRTI diagnoses were found between HMPV and RSV. Age was an important factor for disease severity among single virus-infected children, where children <6 months old with HMPV had a milder disease than those with RSV, while in children 12–23 months old, the pattern was the opposite. In multivariable logistic regression analysis for each virus type, age ≥12 months (HMPV), and age <6 months (RSV), prematurity, ≥1 chronic disease and high viral loads of RSV, but not high HMPV viral loads, were risk factors for severe disease. Conclusions Among hospitalized children with LRTI, HMPV manifests independently of viral co-detections and HMPV genotypes. Disease severity in HMPV- and RSV-infected children varies in relation to age. A history of prematurity and chronic disease increases the risk of severe LRTI among HMPV- and RSV-infected children. PMID:28095451

  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 infection in infants admitted to paediatric intensive care units in London, and in their families.

    Science.gov (United States)

    Crowcroft, N S; Zambon, M; Harrison, T G; Mok, Q; Heath, P; Miller, E

    2008-04-01

    We carried out a study in five London paediatric intensive care units (PICUs), with the objectives of describing a cohort of infants with respiratory syncytial virus (RSV) infection, comparing hospital diagnosis with PCR results and investigating the spread of RSV in families. Eligible infants were under 5 months old and admitted betweem November 1998 and October 1999 with respiratory failure, apnoea and/or bradycardia or acute life threatening episodes (ALTE). We diagnosed RSV by PCR analysis of nasopharyngeal aspirate, and in contacts by PCR of pernasal swabs. Of the 137 eligible infants, 66% (91/137) were recruited; of these, 82% (75/91) had RSV, with 47% (35/75) diagnosed by hospital laboratory tests and 93% (70/75) by PCR. The median duration of ventilation was 4.4 days, the length of stay on PICU, 8.6 days, and the length of stay in hospital, 15.9 days. In most families (62%), the parents and siblings developed symptoms of RSV infection at the same time as the infant. When the index infant was a secondary case, primary cases occurred in both older siblings (16 families) and adults (11 families). Silent RSV infection occurred frequently amongst children and adults. RSV is under-diagnosed in PICUs. PCR increases the rate of diagnosis of RSV compared to routine hospital diagnostic methods. Young infants are most often infected at the same time as or before their parents and siblings, indicating that the source may be outside the household; vaccinating family members may not prevent RSV infection in infants.

  4. Epidemiology and Clinical Presentations of Respiratory Syncytial Virus Subgroups A and B Detected with Multiplex Real-Time PCR

    Science.gov (United States)

    Liu, Wenkuan; Chen, Dehui; Tan, Weiping; Xu, Duo; Qiu, Shuyan; Zeng, Zhiqi; Li, Xiao; Zhou, Rong

    2016-01-01

    Respiratory syncytial virus (RSV) is one of the most important pathogenic infections of children and requires in-depth research worldwide, and especially in developing countries. We used a novel multiplex real-time PCR to test 5483 patients (≤ 14 years old) hospitalized with respiratory illness in Guangzhou, China, over a 3-year period. Of these patients, 729 were positive for RSV-A (51.2%, 373/729) or RSV-B (48.8%, 356/729), but none was infected with both viruses. Two seasonal peaks in total RSV were detected at the changes from winter to spring and from summer to autumn. RSV-B was dominant in 2013 and RSV-A in 2015, whereas RSV-A and RSV-B cocirculated in 2014. The clinical presentations of 645 RSV-positive patients were analyzed. Bronchiolitis, dyspnea, coryza, vomiting, poor appetite, and diarrhea occurred more frequently in RSV-A-positive than RSV-B-positive patients, whereas chill, headache, myalgia, debility, and rash etc. were more frequent in RSV-B-positive than RSV-A-positive patients, suggesting specific clinical characteristics for RSV-A and RSV-B. Coinfectons with other pathogens were common and diverse. Bronchiolitis, fever (≥ 38°C), and poor appetite were more frequent in patients with single RSV infections than in coinfected patients, suggesting the key pathogenic activity of RSV. Analysis of the relationships between the comparative viral load and clinical presentations showed significant differences in bronchiolitis, fever (≥ 38°C), and rash etc. among patients with different viral loads. This study provides a novel rapid method for detecting RSV subgroups, and provides new insights into the epidemiology and clinical implications of RSV. PMID:27764220

  5. Severe Respiratory Syncytial Virus Bronchiolitis in Infants Is Associated with Reduced Airway Interferon Gamma and Substance P

    Science.gov (United States)

    Semple, Malcolm G.; Dankert, Hinke M.; Ebrahimi, Bahram; Correia, Jailson B.; Booth, J. Angela; Stewart, James P.; Smyth, Rosalind L.; Hart, C. Anthony

    2007-01-01

    Background Severe human respiratory syncytial virus (hRSV) bronchiolitis in previously well infants may be due to differences in the innate immune response to hRSV infection. Aim: to determine if factors mediating proposed mechanisms for severe bronchiolitis differ with severity of disease. Methodology/Principle Findings 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-γ), 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-γ 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-γ and NPA SP. Nasal airway sampling appears to be a useful surrogate for distal airway sampling since concentrations of IFN-γ, SP, IL-9 and viral load in NPA correlate with the same in BAL. Conclusions Our data support two proposed mechanisms for severe hRSV disease; reduced local IFN-γ 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. PMID:17940602

  6. Immunogenicity and protective capacity of a virosomal respiratory syncytial virus vaccine adjuvanted with monophosphoryl lipid A in mice.

    Directory of Open Access Journals (Sweden)

    Tobias Kamphuis

    Full Text Available Respiratory Syncytial Virus (RSV is a major cause of viral brochiolitis in infants and young children and is also a significant problem in elderly and immuno-compromised adults. To date there is no efficacious and safe RSV vaccine, partially because of the outcome of a clinical trial in the 1960s with a formalin-inactivated RSV vaccine (FI-RSV. This vaccine caused enhanced respiratory disease upon exposure to the live virus, leading to increased morbidity and the death of two children. Subsequent analyses of this incident showed that FI-RSV induces a Th2-skewed immune response together with poorly neutralizing antibodies. As a new approach, we used reconstituted RSV viral envelopes, i.e. virosomes, with incorporated monophosphoryl lipid A (MPLA adjuvant to enhance immunogenicity and to skew the immune response towards a Th1 phenotype. Incorporation of MPLA stimulated the overall immunogenicity of the virosomes compared to non-adjuvanted virosomes in mice. Intramuscular administration of the vaccine led to the induction of RSV-specific IgG2a levels similar to those induced by inoculation of the animals with live RSV. These antibodies were able to neutralize RSV in vitro. Furthermore, MPLA-adjuvanted RSV virosomes induced high amounts of IFNγ and low amounts of IL5 in both spleens and lungs of immunized and subsequently challenged animals, compared to levels of these cytokines in animals vaccinated with FI-RSV, indicating a Th1-skewed response. Mice vaccinated with RSV-MPLA virosomes were protected from live RSV challenge, clearing the inoculated virus without showing signs of lung pathology. Taken together, these data demonstrate that RSV-MPLA virosomes represent a safe and efficacious vaccine candidate which warrants further evaluation.

  7. Design and Characterization of Epitope-Scaffold Immunogens That Present the Motavizumab Epitope from Respiratory Syncytial Virus

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-06-28

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a 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 {angstrom} resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required.

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

    Directory of Open Access Journals (Sweden)

    Maarten O Blanken

    Full Text Available 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 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. RESULTS: 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. CONCLUSIONS: 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.

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

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    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.

  10. Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Asuncion Mejias

    2013-11-01

    Full Text Available BACKGROUND: Respiratory syncytial virus (RSV is the leading cause of viral lower respiratory tract infection (LRTI and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV LRTI, and to identify biomarkers that can objectively assess RSV disease severity. METHODS AND FINDINGS: This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135, HRV (n = 30, and influenza (n = 16 LRTI, and healthy age- and sex-matched controls (n = 39. A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US with high sensitivity (94% [95% CI 87%-98%] and specificity (98% [95% CI 88%-99%]. It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo. We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2. CONCLUSIONS: Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues

  11. Immunological Response to Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex: An RNA-Sequence Analysis of the Bronchial Lymph Node Transcriptome.

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    Polyana C Tizioto

    Full Text Available Susceptibility to bovine respiratory disease (BRD is multi-factorial and is influenced by stress in conjunction with infection by both bacterial and viral pathogens. While vaccination is broadly used in an effort to prevent BRD, it is far from being fully protective and cases diagnosed from a combination of observed clinical signs without any attempt at identifying the causal pathogens are usually treated with antibiotics. Dairy and beef cattle losses from BRD are profound worldwide and genetic studies have now been initiated to elucidate host loci which underlie susceptibility with the objective of enabling molecular breeding to reduce disease prevalence. In this study, we employed RNA sequencing to examine the bronchial lymph node transcriptomes of controls and beef cattle which had individually been experimentally challenged with bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Pasteurella multocida, Mannheimia haemolytica or Mycoplasma bovis to identify the genes that are involved in the bovine immune response to infection. We found that 142 differentially expressed genes were located in previously described quantitative trait locus regions associated with risk of BRD. Mutations affecting the expression or amino acid composition of these genes may affect disease susceptibility and could be incorporated into molecular breeding programs. Genes involved in innate immunity were generally found to be differentially expressed between the control and pathogen-challenged animals suggesting that variation in these genes may lead to a heritability of susceptibility that is pathogen independent. However, we also found pathogen-specific expression profiles which suggest that host genetic variation for BRD susceptibility is pathogen dependent.

  12. Respiratory syncytial virus hospitalization risk in the second year of life by specific congenital heart disease diagnoses

    Science.gov (United States)

    Friedman, Deborah; Fryzek, Jon; Jiang, Xiaohui; Bloomfield, Adam; Ambrose, Christopher S.; Wong, Pierre C.

    2017-01-01

    Children with hemodynamically significant congenital heart disease (CHD) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (RSV) disease compared to their healthy peers. Previous studies have demonstrated lower RSV hospitalization risk among all children with CHD at 12–23 months of age versus 0–11 months of age. However, RSV hospitalization risk at 12–23 months of age by specific CHD diagnosis has not been characterized. Both case-control and cohort studies were conducted using data from the US National Inpatient Sample from 1997 to 2013 to characterize relative risk of RSV hospitalization among children 12–23 months of age with CHD. Related CHD diagnoses were combined for analysis. Hospitalizations for RSV and unspecified bronchiolitis were described by length of stay, mechanical ventilation use, mortality, and total charges. Over the 17-year period, 1,168,886 live birth hospitalizations with CHD were identified. Multiple specific CHD conditions had an elevated odds ratio or relative risk of RSV hospitalization. Mean total RSV hospitalization charges were significantly higher among children with CHD relative to those without CHD ($19,650 vs $7,939 in 2015 dollars) for this period. Compared to children without CHD, children with Ebstein’s anomaly, transposition of the great arteries, aortic stenosis, heterotaxia, and aortic arch anomalies had 367-, 344-, 203-, 117- and 47-fold increased risk of inpatient RSV mortality, respectively. Unspecified bronchiolitis hospitalization odds and relative risk across CHD diagnoses were similar to those observed with RSV hospitalization; however, unspecified bronchiolitis hospitalizations were associated with shorter mean days of stay and less frequently associated with mechanical ventilation or mortality. Among children with more severe CHD diagnoses, RSV disease remains an important health risk through the second year of life. These data can help inform decisions regarding

  13. Human respiratory syncytial virus nucleoprotein and inclusion bodies antagonize the innate immune response mediated by MDA5 and MAVS.

    Science.gov (United States)

    Lifland, Aaron W; Jung, Jeenah; Alonas, Eric; Zurla, Chiara; Crowe, James E; Santangelo, Philip J

    2012-08-01

    Currently, the spatial distribution of human respiratory syncytial virus (hRSV) proteins and RNAs in infected cells is still under investigation, with many unanswered questions regarding the interaction of virus-induced structures and the innate immune system. Very few studies of hRSV have used subcellular imaging as a means to explore the changes in localization of retinoic-acid-inducible gene-I (RIG-I)-like receptors or the mitochondrial antiviral signaling (MAVS) protein, in response to the infection and formation of viral structures. In this investigation, we found that both RIG-I and melanoma differentiation-associated gene 5 (MDA5) colocalized with viral genomic RNA and the nucleoprotein (N) as early as 6 h postinfection (hpi). By 12 hpi, MDA5 and MAVS were observed within large viral inclusion bodies (IB). We used a proximity ligation assay (PLA) and determined that the N protein was in close proximity to MDA5 and MAVS in IBs throughout the course of the infection. Similar results were found with the transient coexpression of N and the phosphoprotein (P). Additionally, we demonstrated that the localization of MDA5 and MAVS in IBs inhibited the expression of interferon β mRNA 27-fold following Newcastle disease virus infection. From these data, we concluded that the N likely interacts with MDA5, is in close proximity to MAVS, and localizes these molecules within IBs in order to attenuate the interferon response. To our knowledge, this is the first report of a specific function for hRSV IBs and of the hRSV N protein as a modulator of the innate immune response.

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

    Science.gov (United States)

    Cheung, Michael B.; Sampayo-Escobar, Viviana; Green, Ryan; Moore, Martin L.; Mohapatra, Subhra; Mohapatra, Shyam S.

    2016-01-01

    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. PMID:27695127

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Respiratory syncytial virus hospitalization risk in the second year of life by specific congenital heart disease diagnoses.

    Science.gov (United States)

    Friedman, Deborah; Fryzek, Jon; Jiang, Xiaohui; Bloomfield, Adam; Ambrose, Christopher S; Wong, Pierre C

    2017-01-01

    Children with hemodynamically significant congenital heart disease (CHD) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (RSV) disease compared to their healthy peers. Previous studies have demonstrated lower RSV hospitalization risk among all children with CHD at 12-23 months of age versus 0-11 months of age. However, RSV hospitalization risk at 12-23 months of age by specific CHD diagnosis has not been characterized. Both case-control and cohort studies were conducted using data from the US National Inpatient Sample from 1997 to 2013 to characterize relative risk of RSV hospitalization among children 12-23 months of age with CHD. Related CHD diagnoses were combined for analysis. Hospitalizations for RSV and unspecified bronchiolitis were described by length of stay, mechanical ventilation use, mortality, and total charges. Over the 17-year period, 1,168,886 live birth hospitalizations with CHD were identified. Multiple specific CHD conditions had an elevated odds ratio or relative risk of RSV hospitalization. Mean total RSV hospitalization charges were significantly higher among children with CHD relative to those without CHD ($19,650 vs $7,939 in 2015 dollars) for this period. Compared to children without CHD, children with Ebstein's anomaly, transposition of the great arteries, aortic stenosis, heterotaxia, and aortic arch anomalies had 367-, 344-, 203-, 117- and 47-fold increased risk of inpatient RSV mortality, respectively. Unspecified bronchiolitis hospitalization odds and relative risk across CHD diagnoses were similar to those observed with RSV hospitalization; however, unspecified bronchiolitis hospitalizations were associated with shorter mean days of stay and less frequently associated with mechanical ventilation or mortality. Among children with more severe CHD diagnoses, RSV disease remains an important health risk through the second year of life. These data can help inform decisions regarding interventions to

  18. Novel recombinant DNA vaccine candidates for human respiratory syncytial virus: Preclinical evaluation of immunogenicity and protection efficiency.

    Science.gov (United States)

    Farrag, Mohamed A; Amer, Haitham M; Öhlschläger, Peter; Hamad, Maaweya E; Almajhdi, Fahad N

    2017-03-08

    The development of safe and potent vaccines for human respiratory syncytial virus (HRSV) is still a challenge for researchers worldwide. DNA-based immunization is currently a promising approach that has been used to generate human vaccines for different age groups. In this study, novel HRSV DNA vaccine candidates were generated and preclinically tested in BALB/c mice. Three different versions of the codon-optimized HRSV fusion (F) gene were individually cloned into the pPOE vector. The new recombinant vectors either express full-length (pPOE-F), secretory (pPOE-TF), or M282-90 linked (pPOE-FM2) forms of the F protein. Distinctive expression of the F protein was identified in HEp-2 cells transfected with the different recombinant vectors using ELISA and immunofluorescence. Mice immunization verified the potential for recombinant vectors to elicit significant levels of neutralizing antibodies and CD8(+) T-cell lymphocytes. pPOE-TF showed higher levels of gene expression in cell culture and better induction of the humoral and cellular immune responses. Following virus challenge, mice that had been immunized with the recombinant vectors were able to control virus replication and displayed lower inflammation compared with mice immunized with empty pPOE vector or formalin-inactivated HRSV vaccine. Moreover, pulmonary cytokine profiles of mice immunized with the 3 recombinant vectors were similar to those of the mock infected group. In conclusion, recombinant pPOE vectors are promising HRSV vaccine candidates in terms of their safety, immunogenicity and protective efficiency. These data encourage further evaluation in phase I clinical trials.

  19. Transforming Growth Factor Beta Is a Major Regulator of Human Neonatal Immune Responses following Respiratory Syncytial Virus Infection▿ †

    Science.gov (United States)

    Thornburg, Natalie J.; Shepherd, Bryan; Crowe, James E.

    2010-01-01

    Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T-cell responses may contribute to RSV immunopathology, which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the lungs with a decrease in the blood. Pediatric populations are particularly susceptible to severe RSV infections; however, DC responses to RSV from pediatric populations have not been examined. In this study, primary isolated DCs from cord blood and adult peripheral blood were compared after RSV infection. Transcriptional profiling and biological network analysis identified transforming growth factor beta (TGF-β) and associated signaling molecules as differentially regulated in the two age groups. TGF-β1 was decreased in RSV-infected adult-blood DCs but increased in RSV-infected cord blood DCs. Coculture of adult RSV-infected DCs with autologous T cells induced secretion of gamma interferon (IFN-γ), interleukin 12p70 (IL-12p70), IL-2, and tumor necrosis factor alpha (TNF-α). Conversely, coculture of cord RSV-infected DCs and autologous T cells induced secretion of IL-4, IL-6, IL-1β, and IL-17. Addition of purified TGF-β1 to adult DC-T-cell cocultures reduced secretion of IFN-γ, IL-12p70, IL-2, and TNF-α, while addition of a TGF-β chemical inhibitor to cord DC-T-cell cocultures increased secretion of IL-12p70. These data suggest that TGF-β acts as a major regulator of RSV DC-T-cell responses, which could contribute to immunopathology during infancy. PMID:20926560

  20. Evaluation by Survival Analysis on Effect of Traditional Chinese Medicine in Treating Children with Respiratory Syncytial Viral Pneumonia of Phlegm-Heat Blocking Fei Syndrome

    Institute of Scientific and Technical Information of China (English)

    杨燕; 汪受传; 白文静; 李瑞丽; 艾军

    2009-01-01

    Objective:To objectively evaluate the clinical effect of traditional Chinese medicine in treating children's respiratory syncytial viral pneumonia(RSVP) of phlegm-heat blocking Fei(肺) syndrome(PHBFS). Methods:A single-blinded multi-center,blocked,randomized and parallel-controlled method was adopted.The clinical study was carried out on 206 children with RSVP-PHBFS who were assigned to two groups,108 in the test group treated through intravenous dripping of Qingkailing Injection(清开灵注射液) in combination of...

  1. 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

    . 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...

  2. Long-Term Burden and Respiratory Effects of Respiratory Syncytial Virus Hospitalization in Preterm Infants-The SPRING Study.

    Directory of Open Access Journals (Sweden)

    Xavier Carbonell-Estrany

    Full Text Available The health status of premature infants born 321-350 weeks' gestational age (wGA hospitalized for RSV infection in the first year of life (cases; n = 125 was compared to that of premature infants not hospitalized for RSV (controls; n = 362 through 6 years. The primary endpoints were the percentage of children with wheezing between 2-6 years and lung function at 6 years of age. Secondary endpoints included quality of life, healthcare resource use, and allergic sensitization. A significantly higher proportion of cases than controls experienced recurrent wheezing through 6 years of age (46.7% vs. 27.4%; p = 0.001. The vast majority of lung function tests appeared normal at 6 years of age in both cohorts. In children with pulmonary function in the lower limit of normality (FEV1 Z-score [-2; -1], wheezing was increased, particularly for cases vs. controls (72.7% vs. 18.9%, p = 0.002. Multivariate analysis revealed the most important factor for wheezing was RSV hospitalization. Quality of life on the respiratory subscale of the TAPQOL was significantly lower (p = 0.001 and healthcare resource utilization was significantly higher (p<0.001 in cases than controls. This study confirms RSV disease is associated with wheezing in 32-35 wGA infants through 6 years of age.

  3. 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

    in a three-week period. Sweat and blood samples were obtained at inclusion. The presence of RSV and hMPV RNA was detected using real-time RT-PCR. RESULTS: We detected RSV RNA in 28 saliva specimens, 5 stool samples, and 3 sweat samples. hMPV RNA was detected in one saliva specimen and two sweat samples. Four...... of the five children shedding RNA in faeces had diarrhoea and children shedding RNA in sweat were either less than five weeks of age or had a chronic lung disease. RSV and hMPV RNA was shed in nasal secretions for a median of 11.5 and 5.0 days respectively (p = 0.001). More than 75% of the family members...... 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....

  4. Human respiratory syncytial virus and its vaccine development%人呼吸道合胞病毒及其疫苗研究进展

    Institute of Scientific and Technical Information of China (English)

    胡兵; 方志正

    2013-01-01

    人呼吸道合胞病毒(respiratory syncytial virus,RSV)是引起婴幼儿支气管炎和肺炎的主要病原体.虽然已经过半个多世纪的研究,但至今仍没有安全有效的RSV疫苗上市.科研人员经过几十年的努力,对RSV的分子生物学、流行病学、致病机制等方面的研究已取得重大进展.此文就RSV的病毒学特征、流行病学和疫苗研发策略做一综述.%Human respiratory syncytial virus (RSV) is an important pathogen responsible for bronchitis and pneumonia in young children.No safe and effective vaccines are available so far.Great progress has been made in molecular biology,epidemiology,and pathogenic mechanism of RSV during the past several decades.In this paper,virological and epidemiological characteristics,and vaccine development strategies of RSV are reviewed.

  5. 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.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  8. Dual effects of respiratory syncytial virus infections on airway inflammation by regulation of Th17/Treg responses in ovalbumin-challenged mice.

    Science.gov (United States)

    Wang, Jia; Kong, Lingwen; Luo, Qingli; Li, Bei; Wu, Jinfeng; Liu, Baojun; Wu, Xiao; Dong, Jingcheng

    2014-12-01

    We investigated the effects of respiratory syncytial virus (RSV) infections on ovalbumin (OVA)-challenged mice via regulation of Th17/Treg cell responses. BALB/c mice were challenged with OVA, followed by RSV infections twice. In OVA-challenged mice, the secretion of Th2/Th17-type cytokines, airway hyperresponsiveness and inflammation were significantly inhibited by initial RSV infection. Moreover, the in vivo findings demonstrated that initial RSV infection reversed the imbalance of Th17/Treg responses. In contrast, RSV re-infection strengthened Th2/Th17-type cytokine secretion, airway hyperresponsiveness, and inflammation, especially for lymphocyte infiltration in OVA-challenged mice. Meanwhile, RSV re-infection enhanced the imbalanced Th17/Treg responses. Upon all results reveal that RSV-induced respiratory infections may lead to dual effects pertaining to allergic airway inflammation by regulation of Th17/Treg responses.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. The role of TLR4 and CD14 polymorphisms in the pathogenesis of respiratory syncytial virus bronchiolitis in greek infants.

    Science.gov (United States)

    Goutaki, M; Haidopoulou, K; Pappa, S; Tsakiridis, P; Frydas, E; Eboriadou, M; Hatzistylianou, M

    2014-01-01

    Clinical manifestations of respiratory syncytial virus (RSV) infection vary from minimal disease to severe acute bronchiolitis. The structural complex of TLR4/CD14 participates in the virus recognition as a component of natural immune response. Genetic variations of TLR4/CD14 may explain great variations in disease severity. The aim of this study was to investigate the possible role of polymorphisms of TLR4, Asp299Gly and Thr399Ile and CD14, C-159T and C-550T in the development of RSV bronchiolitis. Our study included two groups of Greek infants and young children (A and B). Group A consisted of 50 infants ≤2 years of age hospitalised with bronchiolitis and group B of 99 previously healthy children aged 4-14 years (control group) with a free past medical history. RSV was identified by PCR of genetic material that was extracted from nasopharyngeal samples collected from all patients. Blood samples were used to extract DNA and by using the PCR-RFLP method we performed TLR4 and CD14 genotyping. We found no association between TLR4 polymorphisms (Asp299Gly and Thr399Ile) and the development of acute bronchiolitis. For CD14 polymorphisms, a positive association was found between the C-159T and the development of bronchiolitis (p=0.05) but not for the other loci. There were no differences detected in the frequencies of the four polymorphisms studied among infants with RSV and non-RSV bronchiolitis. It is concluded that protein CD14 may have a functional role in the viral conjunction to the structural complex TLR4/CD14. The association between the polymorphism C-159T and the manifestation of disease found in our study points out that the severity in the development of acute bronchiolitis is not specified exclusively by the pathogen, but the immune response of the host also plays a significant role. More extensive multicentric studies need to take place, in order to lead to safer conclusions.

  11. Histophilus somni biofilm formation in cardiopulmonary tissue of the bovine host following respiratory challenge

    DEFF Research Database (Denmark)

    Sandal, Indra; Shao, Jian Q.; Annadata, Satish

    2009-01-01

    Biofilms form in a variety of host sites following infection with many bacterial species. However, the study of biofilms in a host is hindered due to the lack of protocols for the proper experimental investigation of biofilms in vivo. Histophilus somni is an agent of respiratory and systemic...... diseases in bovines, and readily forms biofilms in vitro. In the present study the capability of H. somni to form biofilms in cardiopulmonary tissue following experimental respiratory infection in the bovine host was examined by light microscopy, transmission electron microscopy, immunoelectron microscopy...... haemagglutinin (FHA), predicted to be involved in attachment. Thus, this investigation demonstrated that H. somni is capable of forming a biofilm in its natural host, that such a biofilm may be capable of harboring other bovine respiratory disease pathogens, and that the genes responsible for biofilm formation...

  12. Respiratory Syncytial Virus (RSV)

    Science.gov (United States)

    ... address. Your information: Your recipient's information: Your personal message: Thank you! Your e-mail was sent. Save ... term pregnancies and healthy babies. If something goes wrong, we offer information and comfort to families. We ...

  13. Respiratory Syncytial Virus

    Science.gov (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  14. Development of a multiplex RT-PCR for simultaneous diagnosis of human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV) from clinical specimens.

    Science.gov (United States)

    Dayakar, Seetha; Pillai, Heera R; Thulasi, Vineetha P; Nair, Radhakrishnan R

    2016-12-01

    Human metapneumovirus (HMPV) and human respiratory syncytial virus (HRSV) are ubiquitous respiratory viral pathogens. They belong to the family Paramyxoviridae (subfamily Pneumovirinae) and is responsible for acute respiratory tract infections in children, elderly and immunocompromised patients. We designed and tested a multiplex reverse transcriptase polymerase chain reaction (mRT-PCR) as a cost-effective alternative to real-time PCR and cell culture based detection for HMPV and HRSV. The newly developed PCR was used to screen nasal/throat swab samples from 356 patients with suspected acute respiratory infection attending the Government Medical College, Thiruvananthapuram, Kerala, India. The method was compared with a commercially available kit employing real time PCR, for its sensitivity and specificity. 53 (14.9 %) samples were positive for at least one tested pathogen by mRT-PCR. All except one among the positive samples showed similar pathogen profile when tested using real time PCR. 8 (15.1 %) among these 53 were positive for HRSVA, 33 (62.3 %) positive for HRSVB and 12 (22.6 %) were positive for HMPV. 17 (32.7 %) samples showed co-infections in them. Sensitivity and specificity of the mRT-PCR was comparable to that of the commercial kit. Our findings indicate that this newly developed mRT-PCR can be used as a cost-effective alternative for laboratory diagnosis of HMPV/HRSV infection and will significantly reduce diagnostic costs for these viruses in clinical settings.

  15. Induction of IL-6 and CCL5 (RANTES in human respiratory epithelial (A549 cells by clinical isolates of respiratory syncytial virus is strain specific

    Directory of Open Access Journals (Sweden)

    Levitz Ruth

    2012-09-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the major respiratory pathogen of infants and young children. During each seasonal epidemic, multiple strains of both subgroup A and B viruses circulate in the community. Like other RNA viruses, RSV genome replication is prone to errors that results in a heterogeneous population of viral strains some of which may possess differences in virulence. We sought to determine whether clinical isolates of RSV differ in their capacity to induce inflammatory cytokines IL-6 and CCL5 (previously known as RANTES [regulated upon activation, normal T-cell expressed and secreted protein], which are known to be induced in vitro and in vivo in response to RSV, during infection of A549 cells. Results Screening of subgroup A and B isolates revealed heterogeneity among strains to induce IL-6 and CCL5. We chose two subgroup B strains, New Haven (NH1067 and NH1125, for further analysis because of their marked differences in cytokine inducing properties and because subgroup B strains, in general, are less genetically heterogeneous as compared to subgroup A strains. At 12 and 24 hours post infection RSV strains, NH1067 and NH1125 differed in their capacity to induce IL-6 by an order of magnitude or more. The concentrations of IL-6 and CCL5 were dependent on the dose of infectious virus and the concentration of these cytokines induced by NH1125 was greater than that of those induced by NH1067 when the multiplicity of infection of NH1067 used was as much as 10-fold higher than that of NH1125. The induction of IL-6 was dependent on viable virus as infection with UV-inactivated virus did not induce IL-6. The difference in IL-6 induction most likely could not be explained by differences in viral replication kinetics. The intracellular level of RSV RNA, as determined by quantitative RT-PCR, was indistinguishable between the 2 strains though the titer of progeny virus produced by NH1125 was greater than that produced by

  16. Identification of cellular proteins that interact with Newcastle Disease Virus and human Respiratory Syncytial Virus by a two-dimensional virus overlay protein binding assay (VOPBA).

    Science.gov (United States)

    Holguera, Javier; Villar, Enrique; Muñoz-Barroso, Isabel

    2014-10-13

    Although it is well documented that the initial attachment receptors for Newcastle Disease Virus (NDV) and Respiratory Syncytial Virus (RSV) are sialic acid-containing molecules and glycosaminoglycans respectively, the exact nature of the receptors for both viruses remains to be deciphered. Moreover, additional molecules at the host cell surface might be involved in the entry mechanism. With the aim of identifying the cellular proteins that interact with NDV and RSV at the cell surface, we performed a virus overlay protein binding assay (VOPBA). Cell membrane lysates were separated by two dimensional (2D) gel electrophoresis and electrotransferred to PVDF membranes, after which they were probed with high viral concentrations. NDV interacted with a Protein Disulfide Isomerase from chicken fibroblasts. In the case of RSV, we detected 15 reactive spots, which were identified as six different proteins, of which nucleolin was outstanding. We discuss the possible role of PDI and nucleolin in NDV and RSV entry, respectively.

  17. 呼吸道合胞病毒F蛋白研究进展%The research pogress in fusion glycoprotein of human respiratory syncytial virus

    Institute of Scientific and Technical Information of China (English)

    袁媛

    2009-01-01

    The fusion glycoprotein (F) of human respiratory syncytial vires(RSV) is an important viral envelop protein which can induce protective immunity against RSV infection.The structural and functional characteristics of F protein play a central role in the understanding of infection and immunity,and in the development of vaccine.%人呼吸道合胞病毒(RSV)融合蛋白(F蛋白)为病毒表面结构蛋白,可以刺激机体产生保护性抗体和细胞免疫反应.因此对F蛋白的深入研究将有助于了解病毒感染的机理,从而为研究RSV的免疫机理、研制特定部位的亚单位或多肽疫苗提供帮助.

  18. Downregulation of IL7R, CCR7, and TLR4 in the cord blood of children with respiratory syncytial virus disease.

    Science.gov (United States)

    Inchley, Christopher S; Osterholt, Helene C D; Sonerud, Tonje; Fjærli, Hans O; Nakstad, Britt

    2013-11-01

    The association between gene expression at birth of 11 candidate genes with important innate and adaptive immune functions and later respiratory syncytial virus (RSV) disease was investigated. Cord blood was collected from 2108 newborns. Forty-seven were subsequently RSV positive. Gene expression analysis by quantitative reverse transcription-polymerase chain reaction was compared to 17 controls. There was downregulation of interleukin 7 receptor (IL7R) (P = .0001) and chemokine receptor 7 (CCR7) (P = .002), and in the severe disease subcategory, downregulation of Toll-like receptor 4 (TLR4) (P = .003). IL7R and CCR7 facilitate communication between adaptive and innate immune systems. TLR4 activates the innate immune system on RSV exposure. Delayed innate and adaptive immune activation may predispose children to more severe RSV disease.

  19. 呼吸道合胞病毒感染的免疫应答效应%Immune response of respiratory syncytial virus infection

    Institute of Scientific and Technical Information of China (English)

    方青

    2013-01-01

    人呼吸道合胞病毒(respiratory syncytial virus,RSV)是婴幼儿毛细支气管炎的主要病原体,RSV感染是导致儿童以及老年人和免疫缺陷的成年人患病和死亡的主要原因.近来,越来越多的研究发现天然免疫应答以及炎症的异常调节是导致病毒感染后出现病理学效应的重要原因.被动免疫抗体能对感染起一定的预防作用,但自然感染RSV诱发的抗体水平的保护作用较差.RSV感染后机体的免疫应答仍需进一步研究,以加速相关疫苗及毛细支气管炎新疗法的研发.%Human respiratory syncytial virus (RSV) is a main pathogen of bronchiolitis in infants,and RSV infection is a major cause of morbidity and mortality in children,the elderly and immunocompromised adults.Recent studies increasingly emphasize the innate immune responses and the dysregulation of inflammation as key factors in causing pathological effects of infection.The passive antibody can protect against infection,but the antibody levels induced by natural RSV infection are poorly protective.Improved understanding of human immune response to RSV infection continues to be needed in order to accelerate the development of vaccines and new treatments for bronchiolitis.

  20. Enhanced immunogenicity of a respiratory syncytial virus (RSV) F subunit vaccine formulated with the adjuvant GLA-SE in cynomolgus macaques.

    Science.gov (United States)

    Patton, Kathryn; Aslam, Shahin; Shambaugh, Cindy; Lin, Rui; Heeke, Darren; Frantz, Chris; Zuo, Fengrong; Esser, Mark T; Paliard, Xavier; Lambert, Stacie L

    2015-08-26

    Respiratory syncytial virus (RSV) causes significant disease in elderly adults, but an effective vaccine is not yet available. We have previously reported that vaccines consisting of engineered respiratory syncytial virus soluble fusion protein (RSV sF) adjuvanted with glucopyranosyl lipid A (GLA) in an oil-in-water emulsion (stable emulsion [SE]) induce RSV F-specific T and B cell responses in mice and rats that protect from viral challenge. Here, we evaluated the immunogenicity of GLA-SE adjuvanted RSV sF vs unadjuvanted RSV sF vaccines in cynomolgus macaques (Macaca fascicularis). RSV F-specific IgG, RSV neutralizing antibodies, and RSV F-specific T cell IFNγ ELISPOT responses induced by GLA-SE adjuvanted RSV sF peaked at week 6 at significantly higher levels than achieved by unadjuvanted RSV sF and remained detectable through week 24, demonstrating response longevity. Two weeks after a week 24 booster immunization, humoral and cellular responses reached levels similar to those seen at the earlier peak response. Importantly, the GLA-SE adjuvanted RSV sF vaccine induced cross-neutralizing antibodies to other RSV A and B strains as well as F-specific IgA and IgG memory B cells. GLA-SE adjuvanted RSV sF was also demonstrated to drive a Th1-biased response characterized by more IFNγ than IL-4. This study indicates that a GLA-SE adjuvanted RSV sF vaccine induces robust humoral and Th1-biased cellular immunity in non-human primates and may benefit human populations at risk for RSV disease.

  1. Opposing roles of membrane and soluble forms of the receptor for advanced glycation end products in primary respiratory syncytial virus infection.

    Science.gov (United States)

    Miller, Allison L; Sims, Gary P; Brewah, Yambasu A; Rebelatto, Marlon C; Kearley, Jennifer; Benjamin, Ebony; Keller, Ashley E; Brohawn, Philip; Herbst, Ronald; Coyle, Anthony J; Humbles, Alison A; Kolbeck, Roland

    2012-04-15

    Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager(-/-)) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflammatory cytokines, and a reduction in viral load. To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager(-/-) mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager(-/-) mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection.

  2. A Recombinant G Protein Plus Cyclosporine A-Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease.

    Science.gov (United States)

    Li, Chaofan; Zhou, Xian; Zhong, Yiwei; Li, Changgui; Dong, Aihua; He, Zhonghuai; Zhang, Shuren; Wang, Bin

    2016-02-15

    Respiratory syncytial virus (RSV) infection can cause severe disease in the lower respiratory tract of infants and older people. Vaccination with a formalin-inactivated RSV vaccine (FI-RSV) and subsequent RSV infection has led to mild to severe pneumonia with two deaths among vaccinees. The vaccine-enhanced disease (VED) was recently demonstrated to be due to an elevated level of Th2 cell responses following loss of regulatory T (Treg) cells from the lungs. To induce high levels of neutralizing Abs and minimize pathogenic T cell responses, we developed a novel strategy of immunizing animals with a recombinant RSV G protein together with cyclosporine A. This novel vaccine induced not only a higher level of neutralizing Abs against RSV infection, but, most importantly, also significantly higher levels of Treg cells that suppressed VED in the lung after RSV infection. The induced responses provided protection against RSV challenge with no sign of pneumonia or bronchitis. Treg cell production of IL-10 was one of the key factors to suppress VED. These finding indicate that G protein plus cyclosporine A could be a promising vaccine against RSV infection in children and older people.

  3. Induction, duration, and resolution of airway goblet cell hyperplasia in a murine model of atopic asthma: effect of concurrent infection with respiratory syncytial virus and response to dexamethasone.

    Science.gov (United States)

    Blyth, D I; Pedrick, M S; Savage, T J; Bright, H; Beesley, J E; Sanjar, S

    1998-07-01

    We recently described a murine model of atopic asthma in which a marked, extensive hyperplasia of airway goblet cells is induced by repeated challenge of ovalbumin (OA)-sensitized mice with intratracheally administered allergen (Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). We report here the time course of the duration of this feature and of its spontaneous resolution in the absence of further allergen exposure. Induction of severe neutrophilic inflammation in the airways by repeated intratracheal administration of lipopolysaccharide failed to induce goblet cell hyperplasia (GCH) to as great a degree as that induced by allergen, suggesting that nonallergic inflammation is a relatively poor inducer of this phenotype change in mice. When a "subclinical" infection of the lungs with the human A2 strain of respiratory syncytial virus was superimposed on the model of atopic asthma, recruitment of monocytes and lymphocytes to the airways was enhanced and a discharge of goblet cell mucin contents was observed. This may partly explain the respiratory difficulty that typifies virally induced exacerbations of asthma in humans. Daily systemic treatment of sensitized mice with dexamethasone during the period of allergen challenge produced a dose-related suppression of developing GCH, while similar treatment during the period following the establishment of extensive hyperplasia induced an accelerated resolution toward a normal epithelial phenotype. These results confirm and extend the relevance of this model as a representation of the human disease.

  4. In Vitro Activity and Rodent Efficacy of Clinafloxacin For Bovine and Swine Respiratory Disease

    Directory of Open Access Journals (Sweden)

    Michael T Sweeney

    2013-06-01

    Full Text Available Clinafloxacin is a broad-spectrum fluoroquinolone that was originally developed and subsequently abandoned in the late 1990s as a human health antibiotic for respiratory diseases. The purpose of this study was to investigate the activity of clinafloxacin as a possible treatment for respiratory disease in cattle and pigs. MIC values were determined using CLSI recommended procedures with recent strains from the Zoetis culture collection. Rodent efficacy was determined in CD-1 mice infected systemically or intranasally with bovine M. haemolytica or P. multocida, or swine A. pleuropneumoniae, and administered clinafloxacin for determination of ED50s. The MIC90 values for clinafloxacin against bovine P. multocida, M. haemolytica, H. somni and M. bovis were 0.125, 0.5, 0.125 and 1 µg/ml, respectively, and the MIC90 values against swine P. multocida, A. pleuropneumoniae, S. suis, and M. hyopneumoniae were ≤0.03, ≤0.03, 0.125 and ≤0.008 µg/ml, respectively. Efficacy in mouse models showed average ED50s of 0.019 mg/kg/dose in the bovine M. haemolytica systemic infection model, 0.55 mg/kg in the bovine P. multocida intranasal lung challenge model, 0.08 mg/kg/dose in the bovine P. multocida systemic infection model, and 0.7 mg/kg/dose in the swine A. pleuropneumoniae systemic infection model. Clinafloxacin shows good in vitro activity and efficacy in mouse models and may be a novel treatment alternative for the treatment of respiratory disease in cattle and pigs.

  5. In vitro activity and rodent efficacy of clinafloxacin for bovine and swine respiratory disease.

    Science.gov (United States)

    Sweeney, Michael T; Quesnell, Rebecca; Tiwari, Raksha; Lemay, Mary; Watts, Jeffrey L

    2013-01-01

    Clinafloxacin is a broad-spectrum fluoroquinolone that was originally developed and subsequently abandoned in the late 1990s as a human health antibiotic for respiratory diseases. The purpose of this study was to investigate the activity of clinafloxacin as a possible treatment for respiratory disease in cattle and pigs. Minimum inhibitory concentration (MIC) values were determined using Clinical and Laboratory Standards Institute recommended procedures with recent strains from the Zoetis culture collection. Rodent efficacy was determined in CD-1 mice infected systemically or intranasally with bovine Mannheimia haemolytica or Pasteurella multocida, or swine Actinobacillus pleuropneumoniae, and administered clinafloxacin for determination of ED50 (efficacious dose-50%) values. The MIC90 values for clinafloxacin against bovine P. multocida, M. haemolytica, Histophilus somni, and M. bovis were 0.125, 0.5, 0.125, and 1 μg/ml, respectively, and the MIC90 values against swine P. multocida, A. pleuropneumoniae, S. suis, and M. hyopneumoniae were í0.03, í0.03, 0.125, and í0.008 μg/ml, respectively. Efficacy in mouse models showed average ED50 values of 0.019 mg/kg/dose in the bovine M. haemolytica systemic infection model, 0.55 mg/kg in the bovine P. multocida intranasal lung challenge model, 0.08 mg/kg/dose in the bovine P. multocida systemic infection model, and 0.7 mg/kg/dose in the swine A. pleuropneumoniae systemic infection model. Clinafloxacin shows good in vitro activity and efficacy in mouse models and may be a novel treatment alternative for the treatment of respiratory disease in cattle and pigs.

  6. Expression of the Bovine NK-Lysin Gene Family and Activity against Respiratory Pathogens

    Science.gov (United States)

    Chen, Junfeng; Yang, Chingyuan; Tizioto, Polyana C.; Huang, Huan; Lee, Mi O. K.; Payne, Harold R.; Lawhon, Sara D.; Schroeder, Friedhelm; Taylor, Jeremy F.; Womack, James E.

    2016-01-01

    Unlike the genomes of many mammals that have a single NK-lysin gene, the cattle genome contains a family of four genes, one of which is expressed preferentially in the lung. In this study, we compared the expression of the four bovine NK-lysin genes in healthy animals to animals challenged with pathogens known to be associated with bovine respiratory disease (BRD) using transcriptome sequencing (RNA-seq). The expression of several NK-lysins, especially NK2C, was elevated in challenged relative to control animals. The effects of synthetic peptides corresponding to functional region helices 2 and 3 of each gene product were tested on both model membranes and bio-membranes. Circular dichroism spectroscopy indicated that these peptides adopted a more helical secondary structure upon binding to an anionic model membrane and liposome leakage assays suggested that these peptides disrupt membranes. Bacterial killing assays further confirmed the antimicrobial effects of these peptides on BRD-associated bacteria, including both Pasteurella multocida and Mannhemia haemolytica and an ultrastructural examination of NK-lysin-treated P. multocida cells by transmission electron microscopy revealed the lysis of target membranes. These studies demonstrate that the expanded bovine NK-lysin gene family is potentially important in host defense against pathogens involved in bovine respiratory disease. PMID:27409794

  7. Expression of the Bovine NK-Lysin Gene Family and Activity against Respiratory Pathogens.

    Directory of Open Access Journals (Sweden)

    Junfeng Chen

    Full Text Available Unlike the genomes of many mammals that have a single NK-lysin gene, the cattle genome contains a family of four genes, one of which is expressed preferentially in the lung. In this study, we compared the expression of the four bovine NK-lysin genes in healthy animals to animals challenged with pathogens known to be associated with bovine respiratory disease (BRD using transcriptome sequencing (RNA-seq. The expression of several NK-lysins, especially NK2C, was elevated in challenged relative to control animals. The effects of synthetic peptides corresponding to functional region helices 2 and 3 of each gene product were tested on both model membranes and bio-membranes. Circular dichroism spectroscopy indicated that these peptides adopted a more helical secondary structure upon binding to an anionic model membrane and liposome leakage assays suggested that these peptides disrupt membranes. Bacterial killing assays further confirmed the antimicrobial effects of these peptides on BRD-associated bacteria, including both Pasteurella multocida and Mannhemia haemolytica and an ultrastructural examination of NK-lysin-treated P. multocida cells by transmission electron microscopy revealed the lysis of target membranes. These studies demonstrate that the expanded bovine NK-lysin gene family is potentially important in host defense against pathogens involved in bovine respiratory disease.

  8. Incidence and clinical characteristics of the infection by the respiratory syncytial virus in children admitted in Santa Casa de São Paulo Hospital.

    Science.gov (United States)

    Pecchini, Rogério; Berezin, Eitan N; Felício, Maria C Calahani; Passos, Saulo D; Souza, Maria Cândido O de; Lima, Lourdes Rehder de Andrade Vaz de; Ueda, Mirthes; Matsumoto, Tokiko Kyomen; Durigon, Edison L

    2008-12-01

    The purpose of this study was to identify the rate of infections due to RSV and other viruses in children. In addition we have analyzed demographic data and clinical characteristics of the RSV-positive patients comparing with patients infected by other respiratory viruses. We also described the seasonality of the RSV occurrence in a hospital in São Paulo. Children below 5 years old admitted in Santa Casa de São Paulo Hospital between February 2005 and September 2006 due to acute respiratory infections (ARI) were included. A nasopharyngeal specimens were obtained with sterile No. 5 French feeding catheters as soon as possible (usually within 24 h). Specimens were kept refrigerated at 4 degrees C and transported to Adolfo Lutz Institute, where the indirect immunofluorescent assay was performed. Virus identified by these assay included RSV, Adenovirus, Influenza A and B virus and Parainfluenza 1, 2, and 3. Clinical data from each group was compared. Four hundred and fifty five cases were included in the study, with 30% positive for some type of virus. Viruses that were identified included Respiratory Syncytial Virus (73.03%), Influenza (8.42%), Parainfluenza (8.42%) and Adenovirus (3.37%). We divided the subjects in 3 groups: Group 1 RSV-Positive, Group 2 Other Positive Viruses and Group 3 Negative for Respiratory Virus. Mean age (months) was of 7.5 for RSV-positive children, 7.6 for other viruses, and 8 for negative for respiratory virus. The RSV-Positive Group was significantly younger than the Group Negative for Respiratory Virus (p<0.05). Signs of UAI were more present in the Positive RSV Group (p<0.05). General mortality was of 2.41%. There was a higher incidence of RSV between the months of March and August in the two years of the study. Our study indicates RSV as the most prevalent viral agent in children admitted due to (ARI), especially in infants below 3 months old. We have also found that infections due to RSV can occur in months others than the classic

  9. Incidence and clinical characteristics of the infection by the Respiratory Syncytial Virus in children admitted in Santa Casa de São Paulo Hospital

    Directory of Open Access Journals (Sweden)

    Rogério Pecchini

    2008-12-01

    Full Text Available The purpose of this study was to identify the rate of infections due to RSV and other viruses in children. In addition we have analyzed demographic data and clinical characteristics of the RSV-positive patients comparing with patients infected by other respiratory viruses. We also described the seasonality of the RSV occurrence in a hospital in São Paulo. Children below 5 years old admitted in Santa Casa de S��o Paulo Hospital between February 2005 and September 2006 due to acute respiratory infections (ARI were included. A nasopharyngeal specimens were obtained with sterile No. 5 French feeding catheters as soon as possible (usually within 24 h. Specimens were kept refrigerated at 4ºC and transported to Adolfo Lutz Institute, where the indirect immunofluorescent assay was performed. Virus identified by these assay included RSV, Adenovirus, Influenza A and B virus and Parainfluenza 1, 2, and 3. Clinical data from each group was compared. Four hundred and fifty five cases were included in the study, with 30% positive for some type of virus. Viruses that were identified included Respiratory Syncytial Virus (73.03%, Influenza (8.42%, Parainfluenza (8.42% and Adenovirus (3.37%. We divided the subjects in 3 groups: Group 1 RSV-Positive, Group 2 Other Positive Viruses and Group 3 Negative for Respiratory Virus. Mean age (months was of 7.5 for RSV-positive children, 7.6 for other viruses, and 8 for negative for respiratory virus. The RSV-Positive Group was significantly younger than the Group Negative for Respiratory Virus (p<0.05. Signs of UAI were more present in the Positive RSV Group (p<0.05. General mortality was of 2.41%. There was a higher incidence of RSV between the months of March and August in the two years of the study. Our study indicates RSV as the most prevalent viral agent in children admitted due to (ARI, especially in infants below 3 months old. We have also found that infections due to RSV can occur in months others than the

  10. Insurance Status and the Risk of Severe Respiratory Syncytial Virus Disease in United States Preterm Infants Born at 32–35 Weeks Gestational Age

    Science.gov (United States)

    Franklin, Jeremy A.; Anderson, Evan J.; Wu, Xionghua; Ambrose, Christopher S.; Simões, Eric A. F.

    2016-01-01

    Background. Database studies have identified that public health insurance status is associated with an increased risk of severe respiratory syncytial virus (RSV) disease in US infants. However, these studies did not adjust for the presence of other risk factors and did not evaluate the risk in preterm infants. Methods. In this study, we evaluate the independent association between public insurance and severe RSV disease outcomes adjusting for other risk factors. The prospective, observational RSV Respiratory Events among Preterm Infants Outcomes and Risk Tracking (REPORT) study was conducted over 2 consecutive RSV seasons at 188 US clinical sites that enrolled preterm infants born at 32–35 wGA who had not received RSV immunoprophylaxis with palivizumab. Adjusted incidence rates per 100 infant-seasons of the RSV-associated endpoints of outpatient lower respiratory tract infection (LRI), emergency department (ED) visits, RSV hospitalizations (RSVHs), and intensive care unit admissions during peak RSV season (November–March) were compared for infants with private and public insurance. Results. Of 1642 evaluable infants enrolled in the REPORT study, 50.1% had private insurance and 49.9% had public health insurance. Adjusted rates of RSV outpatient LRIs were similar; however, rates of ED visits (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.20–3.45) were higher for subjects with public insurance, with a similar but nonsignificant trend observed for hospitalization (HR, 1.61; 95% CI, .93–2.78). Conclusions. Socioeconomic status, as evaluated by public versus private healthcare insurance, is a significant independent risk factor for ED use in US preterm infants and may contribute to increased RSVHs in this population. PMID:27704018

  11. TLR4 Asp299Gly and Thr399Ile polymorphisms: no impact on human immune responsiveness to LPS or respiratory syncytial virus.

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    Renée N Douville

    Full Text Available BACKGROUND: A broad variety of natural environmental stimuli, genotypic influences and timing all contribute to expression of protective versus maladaptive immune responses and the resulting clinical outcomes in humans. The role of commonly co-segregating Toll-like receptor 4 (TLR4 non-synonymous single nucleotide polymorphisms Asp299Gly and Thr399Ile in this process remains highly controversial. Moreover, what differential impact these polymorphisms might have in at risk populations with respiratory dysfunction, such as current asthma or a history of infantile bronchiolitis, has never been examined. Here we determine the importance of these polymorphisms in modulating LPS and respiratory syncytial virus (RSV--driven cytokine responses. We focus on both healthy children and those with clinically relevant respiratory dysfunction. METHODOLOGY: To elucidate the impact of TLR4 Asp299Gly and Thr399Ile on cytokine production, we assessed multiple immune parameters in over 200 pediatric subjects aged 7-9. Genotyping was followed by quantification of pro- and anti-inflammatory cytokine responses by fresh peripheral blood mononuclear cells upon acute exposure to LPS or RSV. PRINCIPAL FINDINGS: In contrast to early reports, neither SNP influenced immune responses evoked by LPS exposure or RSV infection, as measured by the intermediate phenotype of pro- and anti-inflammatory cytokine responses to these ubiquitous agents. There is no evidence of altered sensitivity in populations with "at risk" clinical phenotypes. CONCLUSIONS/SIGNIFICANCE: Genomic medicine seeks to inform clinical practice. Determination of the TLR4 Asp299Gly/Thr399Ile haplotype is of no clinical benefit in predicting the nature or intensity of cytokine production in children whether currently healthy or among specific at-risk groups characterized by prior infantile broncholitis or current asthma.

  12. Insurance Status and the Risk of Severe Respiratory Syncytial Virus Disease in United States Preterm Infants Born at 32-35 Weeks Gestational Age.

    Science.gov (United States)

    Franklin, Jeremy A; Anderson, Evan J; Wu, Xionghua; Ambrose, Christopher S; Simões, Eric A F

    2016-09-01

    Background.  Database studies have identified that public health insurance status is associated with an increased risk of severe respiratory syncytial virus (RSV) disease in US infants. However, these studies did not adjust for the presence of other risk factors and did not evaluate the risk in preterm infants. Methods.  In this study, we evaluate the independent association between public insurance and severe RSV disease outcomes adjusting for other risk factors. The prospective, observational RSV Respiratory Events among Preterm Infants Outcomes and Risk Tracking (REPORT) study was conducted over 2 consecutive RSV seasons at 188 US clinical sites that enrolled preterm infants born at 32-35 wGA who had not received RSV immunoprophylaxis with palivizumab. Adjusted incidence rates per 100 infant-seasons of the RSV-associated endpoints of outpatient lower respiratory tract infection (LRI), emergency department (ED) visits, RSV hospitalizations (RSVHs), and intensive care unit admissions during peak RSV season (November-March) were compared for infants with private and public insurance. Results.  Of 1642 evaluable infants enrolled in the REPORT study, 50.1% had private insurance and 49.9% had public health insurance. Adjusted rates of RSV outpatient LRIs were similar; however, rates of ED visits (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.20-3.45) were higher for subjects with public insurance, with a similar but nonsignificant trend observed for hospitalization (HR, 1.61; 95% CI, .93-2.78). Conclusions.  Socioeconomic status, as evaluated by public versus private healthcare insurance, is a significant independent risk factor for ED use in US preterm infants and may contribute to increased RSVHs in this population.

  13. Respiratory syncytial virus hospitalizations in infants of 28 weeks gestational age and less in the palivizumab era

    Directory of Open Access Journals (Sweden)

    Bernhard Resch

    2017-04-01

    Conclusions: Despite palivizumab prophylaxis the burden of RSV disease and all cause respiratory illness was still remarkable in this vulnerable preterm population and mainly limited to the first season.

  14. Association between Respiratory Syncytial Virus Activity and Pneumococcal Disease in Infants: A Time Series Analysis of US Hospitalization Data

    OpenAIRE

    Weinberger, Daniel M.; Klugman, Keith P.; Steiner, Claudia A.; Lone Simonsen; Cécile Viboud

    2015-01-01

    Editors' Summary Background Respiratory infections—bacterial and viral infections of the lungs and the airways (the tubes that take oxygen-rich air to the lungs)—are major causes of illness and death in children worldwide. Pneumonia (infection of the lungs) alone is responsible for about 15% of all child deaths. The leading cause of bacterial pneumonia in children is Streptococcus pneumoniae, which is transmitted through contact with infected respiratory secretions. S. pneumoniae usually caus...

  15. Epidemiology of respiratory syncytial virus in children in Cyprus during three consecutive winter seasons (2010-2013): age distribution, seasonality and association between prevalent genotypes and disease severity.

    Science.gov (United States)

    Panayiotou, C; Richter, J; Koliou, M; Kalogirou, N; Georgiou, E; Christodoulou, C

    2014-11-01

    This study reports the epidemiology of respiratory syncytial virus (RSV) in hospitalized children in Cyprus over three successive seasons (2010-2013) and the association between prevalent genotypes and disease severity. RSV infections had a circulation pattern from December to March. Most RSV-positive children (83%) were aged <2 years. Genotyping of RSV isolates showed that during the first winter season of the study (2010-2011), the only RSV genotype circulating was GA2 (RSV-A), followed by genotype BA (RSV-B) in the next winter season with only few sporadic cases of GA2. During the last winter season of the study (2012-2013) the newly emerged RSV genotype ON1 (RSV-A) was virtually the only circulating genotype. Children infected with genotype ON1 suffered a significantly milder illness compared to infections with genotypes GA2 and BA with a higher percentage of BA-infected children requiring oxygen. Our findings are in contrast to the majority of published reports that suggest RSV-A causes more severe illness than RSV-B. Therefore, further investigation of the association between RSV genotypes and disease severity is required, as it might affect treatment strategies in the future.

  16. Combination therapy using monoclonal antibodies against respiratory syncytial virus (RSV) G glycoprotein protects from RSV disease in BALB/c mice.

    Science.gov (United States)

    Caidi, Hayat; Harcourt, Jennifer L; Tripp, Ralph A; Anderson, Larry J; Haynes, Lia M

    2012-01-01

    Therapeutic options to control respiratory syncytial virus (RSV) are limited, thus development of new therapeutics is high priority. Previous studies with a monoclonal antibody (mAb) reactive to an epitope proximal to the central conserved region (CCR) of RSV G protein (mAb 131-2G) showed therapeutic efficacy for reducing pulmonary inflammation RSV infection in BALB/c mice. Here, we show a protective effect in RSV-infected mice therapeutically treated with a mAb (130-6D) reactive to an epitope within the CCR of G protein, while treatment with a mAb specific for a carboxyl G protein epitope had no effect. Combined treatment with mAbs 130-6D and 131-2G significantly decreased RSV-associated pulmonary inflammation compared to either antibody alone. The results suggest that anti-RSV G protein mAbs that react at or near the CCR and can block RSV G protein-mediated activities are effective at preventing RSV disease and may be an effective strategy for RSV therapeutic treatment.

  17. A respiratory syncytial virus persistent-infected cell line system reveals the involvement of SOCS1 in the innate antiviral response

    Institute of Scientific and Technical Information of China (English)

    Junwen; Zheng; Pu; Yang; Yan; Tang; Dongchi; Zhao

    2015-01-01

    HEp-2 cells persistently infected with respiratory syncytial virus(RSV) are a heterogeneous mixture of viral antigen-positive and-negative variants; however, the mechanism through which viral replication becomes latent remains unclear. In this study, we investigated the potential mechanism by which RSV escapes from innate immune surveillance. Persistent-infected RSV HEp-2 cells were isolated and cell clones were passaged. The RSV-persistent cells produced viruses at a lower titer, resisted wild-type RSV re-infection, and secreted high levels of interferon-β(IFN-β), macrophage inflammatory protein-1α(Mip-1α), interleukin-8(IL-8), and Rantes. Toll-like receptor 3(TLR3), retinoic acid inducible gene-I(RIG-I), and suppressor of cytokine signaling 1(SOCS1) levels were upregulated in these cells. The silencing of TLR3 m RNA decreased the expression of SOCS1 protein and the secretion of cytokines. RSV-persistent cells are in an inflammatory state; upregulation of SOCS1 is related to the TLR3 signaling pathway, which could be associated with the mechanism of viral persistence.

  18. Effect of Brazilian Propolis on Exacerbation of Respiratory Syncytial Virus Infection in Mice Exposed to Tetrabromobisphenol A, a Brominated Flame Retardant

    Science.gov (United States)

    Takeshita, Tomomi; Toyama, Satomi; Hayashi, Yuya; Honda, Shiori; Sakamoto, Shuichi; Matsuoka, Sayuri; Hidaka, Muneaki; Tsutsumi, Shigetoshi; Yasukawa, Ken; Park, Yong Kun

    2013-01-01

    Tetrabromobisphenol A (TBBPA), a brominated flame retardant, has been found to exacerbate pneumonia in respiratory syncytial virus- (RSV-) infected mice. We examined the effect of Brazilian propolis (AF-08) on the exacerbation of RSV infection by TBBPA exposure in mice. Mice were fed a powdered diet mixed with 1% TBBPA alone, 0.02% AF-08 alone, or 1% TBBPA and 0.02% AF-08 for four weeks and then intranasally infected with RSV. TBBPA exposure increased the pulmonary virus titer and level of IFN-γ, a representative marker of pneumonia due to RSV infection, in the lungs of infected mice without toxicity. AF-08 was significantly effective in reducing the virus titers and IFN-γ level increased by TBBPA exposure. Also, AF-08 significantly reduced proinflammatory cytokine (TNF-α and IL-6) levels in the lungs of RSV-infected mice with TBBPA exposure, but Th2 cytokine (IL-4 and IL-10) levels were not evidently increased. Neither TBBPA exposure nor AF-08 treatment affected the anti-RSV antibody production in RSV-infected mice. In flow cytometry analysis, AF-08 seemed to be effective in reducing the ratio of pulmonary CD8a+ cells in RSV-infected mice with TBBPA exposure. TBBPA and AF-08 did not exhibit anti-RSV activity in vitro. Thus, AF-08 probably ameliorated pneumonia exacerbated by TBBPA exposure in RSV-infected mice by limiting excess cellular immune responses. PMID:24250719

  19. [Development of new approaches to standartization of enzyme immunoassay test systems for detection of antibodies to respiratory syncytial virus using electron microscopy and monoclonal antibodies].

    Science.gov (United States)

    Krivitskaia, V Z; Sirotkin, A K; Samoĭlovich, M P; Sominina, A A

    1999-01-01

    Respiratory syncytial virus (RSV), strain Long, was purified through 20-60% sucrose gradient. The virions from different sucrose density zones were tested by ELISA for reactivity with monoclonal antibodies (MAB) to F- (MAB 9C5) and N- (MAB 8B10) proteins of RSV. Comparative study of the same patterns of RSV by electron microscopy after negative staining showed a close relationship between the virion morphology and MAB binding in ELISA. MAB 9C5 were highly reactive with the surface domains of both mature RSV virions and "empty" virion envelopes without formed inner nucleocapsid structures. MAB 8B10 reacted well only with mature virions with completely assembled nucleocapsids. These MAB failed to reorganize the N-protein epitope of immature and destroyed virions, which indicated a conformation dependence of the 8B10 binding site. For practical purposes, MAB tests can be used to determine the RSV patterns, which can be used in ELISA for serologic diagnosis of RSV infection. Testing with these MAB demonstrate the stability of RSV to extreme exposures (lyophilization, storage, heating), which is important for creation of sensitive ELISA test systems and their standardization.

  20. A mixed treatment comparison meta-analysis of antibiotic treatments for bovine respiratory disease.

    Science.gov (United States)

    O'Connor, Annette M; Coetzee, Johann F; da Silva, Natalia; Wang, Chong

    2013-06-01

    In this publication we use mixed treatment comparison meta-analysis to compare the efficacy of antibiotic treatments for bovine respiratory disease in beef cattle. Studies were eligible for the meta-analysis if they were publically available and reported the assessment of antibiotic protocols registered for use in the United States (US) for bovine respiratory disease (BRD) in beef cattle and were conducted in North America. Three electronic databases, the proceedings of two bovine specific conferences, pharmaceutical company web sites and the US Food and Drug Administration website were searched to identify relevant trials. The network of evidence used in the analysis contained 194 trial arms from 93 trials. Of the 93 trials there were 8 with three arms. The network of evidence contained information for 12 antibiotics. The output from the analysis provided information about the risk ratio comparing all possible treatments for BRD including comparisons based only on indirect data. The output also included a relative ranking of the treatments and estimates of the probability that an antibiotic protocol was the worst treatment option.

  1. Contribution of Fcγ receptors to human respiratory syncytial virus pathogenesis and the impairment of T-cell activation by dendritic cells.

    Science.gov (United States)

    Gómez, Roberto S; Ramirez, Bruno A; Céspedes, Pablo F; Cautivo, Kelly M; Riquelme, Sebastián A; Prado, Carolina E; González, Pablo A; Kalergis, Alexis M

    2016-01-01

    Human respiratory syncytial virus (hRSV) is the leading cause of infant hospitalization related to respiratory disease. Infection with hRSV produces abundant infiltration of immune cells into the airways, which combined with an exacerbated pro-inflammatory immune response can lead to significant damage to the lungs. Human RSV re-infection is extremely frequent, suggesting that this virus may have evolved molecular mechanisms that interfere with host adaptive immunity. Infection with hRSV can be reduced by administering a humanized neutralizing antibody against the virus fusion protein in high-risk infants. Although neutralizing antibodies against hRSV effectively block the infection of airway epithelial cells, here we show that both, bone marrow-derived dendritic cells (DCs) and lung DCs undergo infection with IgG-coated virus (hRSV-IC), albeit abortive. Yet, this is enough to negatively modulate DC function. We observed that such a process is mediated by Fcγ receptors (FcγRs) expressed on the surface of DCs. Remarkably, we also observed that in the absence of hRSV-specific antibodies FcγRIII knockout mice displayed significantly less cellular infiltration in the lungs after hRSV infection, compared with wild-type mice, suggesting a potentially harmful, IgG-independent role for this receptor in hRSV disease. Our findings support the notion that FcγRs can contribute significantly to the modulation of DC function by hRSV and hRSV-IC. Further, we provide evidence for an involvement of FcγRIII in the development of hRSV pathogenesis.

  2. WHO consultation on Respiratory Syncytial Virus Vaccine Development Report from a World Health Organization Meeting held on 23-24 March 2015.

    Science.gov (United States)

    Modjarrad, Kayvon; Giersing, Birgitte; Kaslow, David C; Smith, Peter G; Moorthy, Vasee S

    2016-01-04

    Respiratory syncytial virus (RSV) is a globally prevalent cause of lower respiratory infection in neonates and infants. Despite its disease burden, a safe and effective RSV vaccine has remained elusive. In recent years, improved understanding of RSV biology and innovations in immunogen design has resulted in the advancement of multiple vaccine candidates into the clinical development pipeline. Given the growing number of vaccines in clinical trials, the rapid pace at which they are being tested, and the likelihood that an RSV vaccine will reach the commercial market in the next 5-10 years, consensus and guidance on clinical development pathways and licensure routes are needed now, before large-scale efficacy trials commence. In pursuit of this aim, the World Health Organization convened the first RSV vaccine consultation in 15 years on the 23rd and 24th of March, 2015 in Geneva, Switzerland. The meeting's primary objective was to provide guidance on clinical endpoints and development pathways for vaccine trials with a focus on considerations of low- and middle-income countries. Meeting participants reached consensus on candidate case definitions for RSV disease, considerations for clinical efficacy endpoints, and the clinical development pathway for active and passive immunization trials in maternal and pediatric populations. The strategic focus of this meeting was on the development of high quality, safe and efficacious RSV preventive interventions for global use and included: (1) maternal/passive immunization to prevent RSV disease in infants less than 6 months; (2) pediatric immunization to prevent RSV disease in infants and young children once protection afforded by maternal immunization wanes.

  3. 人呼吸道合胞病毒的研究与防治进展%Advances in Human Respiratory Syncytial Virus Research and Control

    Institute of Scientific and Technical Information of China (English)

    郭恺; 张玉彬

    2013-01-01

    人呼吸道合胞病毒是全世界婴幼儿下呼吸道感染最常见的病原体,导致每年超过300万人住院和20万以上的人死亡,给全球带来了非常严重的经济和社会负担.目前,尚不存在防治RSV的疫苗,也没有特异性强、安全性高的抗RSV药物.对HRSV的结构、流行病学特征以及疾病模型构建方面的研究进展进行综述,并对已有的检测和治疗方法进行总结,旨在为今后开发抗HRSV的药物提供全面的参考信息.%Human respiratory syncytial virus is the most common cause of infection in lower respiratory tract in infants and children around the world,which leads to more than 3 million inpatients and 200 thousand death and brings very serious economic and social burden.So far there are no vaccines or drugs with strong specificity and high safety that can prevent people from RSV infection.The research progress in the structure,epidemiological characteristics and disease modeling of HRSV was reviewed and the existing methods of detection and treatment HRSV were summarized in order to provide a comprehensive reference information for the future development of anti-HRSV drugs.

  4. TLR2/MyD88/NF-κB pathway, reactive oxygen species, potassium efflux activates NLRP3/ASC inflammasome during respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Jesus Segovia

    Full Text Available Human respiratory syncytial virus (RSV constitute highly pathogenic virus that cause severe respiratory diseases in newborn, children, elderly and immuno-compromised individuals. Airway inflammation is a critical regulator of disease outcome in RSV infected hosts. Although "controlled" inflammation is required for virus clearance, aberrant and exaggerated inflammation during RSV infection results in development of inflammatory diseases like pneumonia and bronchiolitis. Interleukin-1β (IL-1β plays an important role in inflammation by orchestrating the pro-inflammatory response. IL-1β is synthesized as an immature pro-IL-1β form. It is cleaved by activated caspase-1 to yield mature IL-1β that is secreted extracellularly. Activation of caspase-1 is mediated by a multi-protein complex known as the inflammasome. Although RSV infection results in IL-1β release, the mechanism is unknown. Here in, we have characterized the mechanism of IL-1β secretion following RSV infection. Our study revealed that NLRP3/ASC inflammasome activation is crucial for IL-1β production during RSV infection. Further studies illustrated that prior to inflammasome formation; the "first signal" constitutes activation of toll-like receptor-2 (TLR2/MyD88/NF-κB pathway. TLR2/MyD88/NF-κB signaling is required for pro-IL-1β and NLRP3 gene expression during RSV infection. Following expression of these genes, two "second signals" are essential for triggering inflammasome activation. Intracellular reactive oxygen species (ROS and potassium (K(+ efflux due to stimulation of ATP-sensitive ion channel promote inflammasome activation following RSV infection. Thus, our studies have underscored the requirement of TLR2/MyD88/NF-κB pathway (first signal and ROS/potassium efflux (second signal for NLRP3/ASC inflammasome formation, leading to caspase-1 activation and subsequent IL-1β release during RSV infection.

  5. 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

  6. Metaphylactic antimicrobial therapy for bovine respiratory disease in stocker and feedlot cattle.

    Science.gov (United States)

    Nickell, Jason S; White, Brad J

    2010-07-01

    This article provides an overview of implementing metaphylactic antimicrobial protocols to certain classes of cattle on arrival to stocker and feedlot production systems. The goal of this management practice is to reduce the negative health and performance effects induced by bovine respiratory disease (BRD). This article emphasizes the multiple factors that influence the decision for mass medication, including weight (age) of the cattle, distance traveled, environmental conditions, previous health history, visual inspection of the cattle at arrival, and prediction of the risk of disease. Current data suggest that metaphylactic programs significantly reduce negative health effects and improve feed performance that can be observed in cattle stricken with BRD.

  7. Respiratory syncytial virus-like nanoparticle vaccination induces long-term protection without pulmonary disease by modulating cytokines and T-cells partially through alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Lee YT

    2015-07-01

    Full Text Available Young-Tae Lee,1,* Eun-Ju Ko,1,2,* Hye Suk Hwang,1,2 Jong Seok Lee,1,3 Ki-Hye Kim,1 Young-Man Kwon,1 Sang-Moo Kang1,2 1Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, 2Department of Biology, Georgia State University, Atlanta, GA, USA; 3National Institute of Biological Resources, Incheon, South Korea *These authors contributed equally to this work Abstract: The mechanisms of protection against respiratory syncytial virus (RSV are poorly understood. Virus-like nanoparticles expressing RSV glycoproteins (eg, a combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs] have been suggested to be a promising RSV vaccine candidate. To understand the roles of alveolar macrophages (AMs in inducing long-term protection, mice that were 12 months earlier vaccinated with formalin-inactivated RSV (FI-RSV or FG VLPs were treated with clodronate liposome prior to RSV infection. FI-RSV immune mice with clodronate liposome treatment showed increases in eosinophils, plasmacytoid dendritic cells, interleukin (IL-4+ T-cell infiltration, proinflammatory cytokines, chemokines, and, in particular, mucus production upon RSV infection. In contrast to FI-RSV immune mice with severe pulmonary histopathology, FG VLP immune mice showed no overt sign of histopathology and significantly lower levels of eosinophils, T-cell infiltration, and inflammatory cytokines, but higher levels of interferon-γ, which are correlated with protection against RSV disease. FG VLP immune mice with depletion of AMs showed increases in inflammatory cytokines and chemokines, as well as eosinophils. The results in this study suggest that FG nanoparticle vaccination induces long-term protection against RSV and that AMs play a role in the RSV protection by modulating eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration. Keywords: alveolar macrophage, nanoparticle vaccine, VLP, FI-RSV, RSV disease

  8. Major Histocompatibility Complex-Dependent Cytotoxic T Lymphocyte Repertoire and Functional Avidity Contribute to Strain-Specific Disease Susceptibility after Murine Respiratory Syncytial Virus Infection ▿

    Science.gov (United States)

    Jessen, Birthe; Faller, Simone; Krempl, Christine D.; Ehl, Stephan

    2011-01-01

    Susceptibility to respiratory syncytial virus (RSV) infection in mice is genetically determined. While RSV causes little pathology in C57BL/6 mice, pulmonary inflammation and weight loss occur in BALB/c mice. Using major histocompatibility complex (MHC)-congenic mice, we observed that the H-2d allele can partially transfer disease susceptibility to C57BL/6 mice. This was not explained by altered viral elimination or differences in the magnitude of the overall virus-specific cytotoxic T lymphocyte (CTL) response. However, H-2d mice showed a more focused response, with 70% of virus-specific CTL representing Vβ8.2+ CTL directed against the immunodominant epitope M2-1 82, while in H-2b mice only 20% of antiviral CTL were Vβ9+ CTL specific for the immunodominant epitope M187. The immunodominant H-2d-restricted CTL lysed target cells less efficiently than the immunodominant H-2b CTL, probably contributing to prolonged CTL stimulation and cytokine-mediated immunopathology. Accordingly, reduction of dominance of the M2-1 82-specific CTL population by introduction of an M187 response in the F1 generation of a C57BL/6N × C57BL/6-H-2d mating (C57BL/6-H-2dxb mice) attenuated disease. Moreover, disease in H-2d mice was less pronounced after infection with an RSV mutant failing to activate M2-1 82-specific CTL or after depletion of Vβ8.2+ cells. These data illustrate how the MHC-determined diversity and functional avidity of CTL responses contribute to disease susceptibility after viral infection. PMID:21795345

  9. A novel respiratory syncytial virus (RSV F subunit vaccine adjuvanted with GLA-SE elicits robust protective TH1-type humoral and cellular immunity in rodent models.

    Directory of Open Access Journals (Sweden)

    Stacie L Lambert

    Full Text Available Illness associated with Respiratory Syncytial Virus (RSV remains an unmet medical need in both full-term infants and older adults. The fusion glycoprotein (F of RSV, which plays a key role in RSV infection and is a target of neutralizing antibodies, is an attractive vaccine target for inducing RSV-specific immunity.BALB/c mice and cotton rats, two well-characterized rodent models of RSV infection, were used to evaluate the immunogenicity of intramuscularly administered RSV vaccine candidates consisting of purified soluble F (sF protein formulated with TLR4 agonist glucopyranosyl lipid A (GLA, stable emulsion (SE, GLA-SE, or alum adjuvants. Protection from RSV challenge, serum RSV neutralizing responses, and anti-F IgG responses were induced by all of the tested adjuvanted RSV sF vaccine formulations. However, only RSV sF + GLA-SE induced robust F-specific TH1-biased humoral and cellular responses. In mice, these F-specific cellular responses include both CD4 and CD8 T cells, with F-specific polyfunctional CD8 T cells that traffic to the mouse lung following RSV challenge. This RSV sF + GLA-SE vaccine formulation can also induce robust RSV neutralizing titers and prime IFNγ-producing T cell responses in Sprague Dawley rats.These studies indicate that a protein subunit vaccine consisting of RSV sF + GLA-SE can induce robust neutralizing antibody and T cell responses to RSV, enhancing viral clearance via a TH1 immune-mediated mechanism. This vaccine may benefit older populations at risk for RSV disease.

  10. A high burden of respiratory syncytial virus associated pneumonia in children less than two years of age in a South East Asian refugee population.

    Directory of Open Access Journals (Sweden)

    Claudia Turner

    Full Text Available BACKGROUND: Pneumonia is a major cause of childhood mortality and morbidity approximately 1.6 million deaths and 150 million episodes occur annually in children <5 years. Respiratory syncytial virus (RSV may be responsible for up to 25% of cases and 12% of deaths making it an important potential vaccine target, although data from South East Asia is scarce. METHODS: We followed a birth cohort of Burmese refugee children, born over a one year period, for two years. Pneumonia episodes were diagnosed using WHO criteria. A chest radiograph, nasopharyngeal aspirate and non-specific markers of infection were taken during each episode. RESULTS: The incidence of RSV-associated pneumonia was 0.24 (95% CI 0.22-0.26 episodes per child year. All children with pneumonia received antibiotic treatment, following WHO guidelines. The highest incidence was in the 2-12 month age group. The commonest diagnosis in a child with RSV-associated pneumonia was non-severe pneumonia (239/362:66.0%, however the incidence of RSV-associated severe or very severe pneumonia was 0.08 (95% CI 0.01-0.10 episodes per child year. Birth in the wet season increased the risk of severe disease in children who had their first episode of RSV-associated pneumonia aged 2-11 months (OR 28.7, 95% CI 6.6-125.0, p<0.001. RSV episodes were highly seasonal being responsible for 80.0% of all the pneumonia episodes occurring each October and November over the study period. CONCLUSIONS: There was a high incidence of RSV associated pneumonia in this refugee population. Interventions to prevent RSV infection have the potential to reduce the incidence of clinically diagnosed pneumonia and hence unnecessary antibiotic usage in this population.

  11. Low CCR7-mediated migration of human monocyte derived dendritic cells in response to human respiratory syncytial virus and human metapneumovirus.

    Directory of Open Access Journals (Sweden)

    Cyril Le Nouën

    2011-06-01

    Full Text Available Human respiratory syncytial virus (HRSV and, to a lesser extent, human metapneumovirus (HMPV and human parainfluenza virus type 3 (HPIV3, can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells (DC is critical in initiating the adaptive immune response. Antigen uptake by DC induces maturational changes that include decreased expression of the chemokine receptors CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and increased expression of CCR7 that mediates the migration of antigen-bearing DC to lymphatic tissue. We stimulated human monocyte-derived DC (MDDC with virus and found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7 expression. Consistent with the differences in CCR7 mRNA and protein expression, MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we showed that the subpopulation of MDDC that was robustly infected with HRSV was particularly inefficient in chemokine receptor modulation. HMPV- or HRSV-stimulated MDDC responded to secondary stimulation with bacterial lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than irreversibly inhibit MDDC migration. This also suggests that the low concentration of proinflammatory cytokines released from HRSV- and HMPV-stimulated MDDC is partly responsible for the low CCR7-mediated migration. We propose that inefficient migration of HRSV- and HMPV-stimulated DC to

  12. 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.

  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.

  14. 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.

  15. Structural Development, Cellular Differentiation and Proliferation of the Respiratory Epithelium in the Bovine Fetal Lung.

    Science.gov (United States)

    Drozdowska, J; Cousens, C; Finlayson, J; Collie, D; Dagleish, M P

    2016-01-01

    Fetal bovine lung samples of 11 different gestational ages were assigned to a classical developmental stage based on histological morphology. Immunohistochemistry was used to characterize the morphology of forming airways, proliferation rate of airway epithelium and the presence of epithelial cell types (i.e. ciliated cells, club cells, neuroepithelial cells (NECs) and type II pneumocytes). Typical structural organization of pseudoglandular (84-98 days gestational age [DGA]), canalicular (154-168 DGA) and alveolar (224-266 DGA) stages was recognized. In addition, transitional pseudoglandular-canalicular (112-126 DGA) and canalicular-saccular (182 DGA) morphologies were present. The embryonic stage was not observed. A significantly (P epithelium, on average 5.5% and 4.4% in bronchi and bronchioles, respectively, was present in the transitional pseudoglandular-canalicular phase (112-126 DGA) compared with all other phases, while from 8 weeks before term (224-266 DGA) proliferation had almost ceased. The first epithelial cells identified by specific marker proteins in the earliest samples available for study (84 DGA) were ciliated cells and NECs. Club cells were present initially at 112 DGA and type II pneumocytes at 224 DGA. At the latest time points (224-226 DGA) these latter cell types were still present at a much lower percentage compared with adult cattle. This study characterized bovine fetal lung development by histological morphology and cellular composition of the respiratory epithelium and suggests that the apparent structural anatomical maturity of the bovine lung at term is not matched by functional maturity of the respiratory epithelium.

  16. Advances in pharmacotherapy of respiratory syncytial virus and rhinovirus infections%呼吸道合胞病毒和鼻病毒呼吸道感染药物治疗进展

    Institute of Scientific and Technical Information of China (English)

    赵宇红; 申昆玲

    2004-01-01

    病毒性呼吸道感染是儿科的常见病、多发病。近年来,对呼吸道病毒感染的防治进行了大量的研究,在治疗呼吸道合胞病毒(Respiratory syncytial vims,RSV)和鼻病毒感染方面出现了一些新的研究成果,现综述如下。

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  19. Safety and Pharmacokinetics of an Intramuscular Monoclonal Antibody (SB 209763) against Respiratory Syncytial Virus (RSV) in Infants and Young Children at Risk for Severe RSV Disease

    Science.gov (United States)

    Meissner, H. Cody; Groothuis, Jessie R.; Rodriguez, William J.; Welliver, Robert C.; Hogg, Geoff; Gray, Peter H.; Loh, Richard; Simoes, Eric A. F.; Sly, Peter; Miller, Ann K.; Nichols, Alice I.; Jorkasky, Diane K.; Everitt, Daniel E.; Thompson, Kathleen A.

    1999-01-01

    We conducted a multicenter, double-blind, placebo-controlled, randomized trial of a humanized monoclonal antibody against a respiratory syncytial virus (RSV) fusion protein (SB 209763) to evaluate its safety, pharmacokinetics, and fusion inhibition and neutralization titers. Forty-three infants who were either delivered prematurely (≤35 weeks’ gestation) or exhibited bronchopulmonary dysplasia were administered either single or repeat (two doses, 8 weeks apart) intramuscular injections of SB 209763 at a concentration of 0.25, 1.25, 5.0, or 10.0 mg/kg or of a placebo. Four of 229 adverse events were considered related to the study drug, including purpura (n = 3) and thrombocytosis (n = 1). No subject developed a detectable level of anti-SB 209763 antibody. Approximately 1 week after administration of the second dose of SB 209763 at 10 mg/kg, the mean plasma concentration (n = 9) was 68.5 μg/ml. The terminal half-life (T1/2) determined by noncompartmental analysis ranged from 22 to 50 days. The population pharmacokinetics for SB 209763 following intramuscular administration was appropriately described by a one-compartment model with first-order input and elimination. Higher values for clearance and volume of distribution at steady state were observed for younger patients, with values decreasing to 0.143 (ml/h)/kg and 161 mL/kg, respectively, by a mean age of 298 days (∼10 months). The mean T1/2 of SB 209763 for the study population was 32.5 days. No other factor (dose, weight, gender, race, premature birth, or bronchopulmonary dysplasia) was observed to alter the population pharmacokinetics of SB 209763 in this study of infants and young children. The mean neutralization titer on day 6 was 286, and the mean fusion inhibition titer was 36. At least 57% of subjects dosed at 1.25 to 10.0 mg of SB 209763 per kg of body weight who were seronegative at baseline experienced a fourfold or greater increase in fusion inhibition titer. Nine RSV infections were documented

  20. Effects of human respiratory syncytial virus, metapneumovirus, parainfluenza virus 3 and influenza virus on CD4+ T cell activation by dendritic cells.

    Directory of Open Access Journals (Sweden)

    Cyril Le Nouën

    Full Text Available BACKGROUND: Human respiratory syncytial virus (HRSV, and to a lesser extent human metapneumovirus (HMPV and human parainfluenza virus type 3 (HPIV3, re-infect symptomatically throughout life without antigenic change, suggestive of incomplete immunity. One causative factor is thought to be viral interference with dendritic cell (DC-mediated stimulation of CD4+ T cells. METHODOLOGY, PRINCIPAL FINDINGS: We infected human monocyte-derived DC with purified HRSV, HMPV, HPIV3, or influenza A virus (IAV and compared their ability to induce activation and proliferation of autologous CD4+ T cells in vitro. IAV was included because symptomatic re-infection without antigenic change is less frequent, suggesting that immune protection is more complete and durable. We examined virus-specific memory responses and superantigen-induced responses by multiparameter flow cytometry. Live virus was more stimulatory than inactivated virus in inducing DC-mediated proliferation of virus-specific memory CD4+ T cells, suggesting a lack of strong suppression by live virus. There were trends of increasing proliferation in the order: HMPVrespiratory viruses are similar in their ability to induce DC to activate CD4+ T cells. Thus, the results do not support the common model in which viral suppression of CD4+ T cell activation and

  1. Influenza and respiratory syncytial virus in infants and children: relationship with attendance at a paediatric emergency unit and characteristics of the circulating strains.

    Science.gov (United States)

    Gasparini, R; Durando, P; Ansaldi, F; Sticchi, L; Banfi, F; Amicizia, D; Panatto, D; Esposito, S; Principi, N; Icardi, G; Crovari, P

    2007-09-01

    A study was carried out on 2,696 Italian children, aged 0-14 years. The goals were: (1) to define the age-related impact of acute respiratory infections (ARI), measured as the risk of attendance at the Paediatric Emergency Room, (2) to better define the importance and proportion of influenza and respiratory syncytial virus (RSV) infections and (3) to acquire deeper knowledge of the influenza strains circulating in infants and children. A standardised emergency unit attendance risk (EUAR) was calculated, by age group for ARI. Specific EUARs were also calculated for the two pathogens. Pharyngeal swabs were tested by polymerase chain reaction (PCR) for influenza and RSVs. Isolation in Madine-Darby canine kidney cells (MDCK) and Hep cells, haemagglutination inhibition (HI) testing and HA1 gene sequence analysis were performed for influenza viruses. Most of the patients enrolled were aged 0-5 years, 1,139 (84.6%) and 1,061 (78.5%) in the two seasons, respectively. The most represented age class was that of 1 year olds (331 cases in 2001-2002 and 301 in 2002-2003). The highest EUAR for ARI was in patients aged 0-3 years (16.8 and 12.9 during the two seasons). The same was observed on calculating this risk by specific pathogens: 17.4 and 5.5 for influenza and 13.0 and 12.7 for RSV. Virological analysis was performed on 2,696 samples, 595 of which proved positive (22%). The highest number of isolates (326) came from patients aged 1-3 years. RSVs were more often identified than influenza viruses in infants aged up to 1 year (32 vs. 20 isolates). Of 265 strains isolated in 2001-2002, 103 were RSVs (87 type A, 16 B) and 162 were influenza (90 type A, 72 B). HI showed that influenza B viruses were related to two lineages, B/Victoria/2/87 (32%) and B/Yamagata/16/88 (68%). Of 330 strains isolated in 2002-2003, 102 were RSVs (91 type A, 11 B) and 228 were influenza viruses (220 type A, 8 B). A/H3N2 strains belonged to two clusters, A/Panama/2007/99-like and A/Fujian/411/02-like

  2. 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

  3. A multicenter, randomized trial comparing synthetic surfactant with modified bovine surfactant extract in the treatment of neonatal respiratory distress syndrome

    NARCIS (Netherlands)

    Adams, E; Vollman, J; Giebner, D; Maurer, M; Dreyer, G; Bailey, L; Anderson, M; Mefford, L; Beaumont, E; Sutton, D; Puppala, B; Mangurten, HH; Secrest, J; Lewis, WJ; Carteaux, P; Bednarek, F; Welsberger, S; Gosselin, R; Pantoja, AF; Belenky, A; Campbell, P; Patole, S; Duenas, M; Kelly, M; Alejo, W; Lewallen, P; DeanLieber, S; Hanft, M; Ferlauto, J; Newell, RW; Bagwell, J; Levine, D; Lipp, RW; Harkavy, K; Vasa, R; Birenbaum, H; Broderick, KA; Santos, AQ; Long, BA; Gulrajani, M; Stern, M; Hopgood, G; Hegyi, T; Alba, J; Christmas, L; McQueen, M; Nichols, N; Brown, M; Quissell, BJ; Rusk, C; Marks, K; Gifford, K; Hoehn, G; Pathak, A; Marino, B; Hunt, P; Fox, [No Value; Sharpstein, C; Feldman, B; Johnson, N; Beecham, J; Balcom, R; Helmuth, W; Boylan, D; Frakes, C; Magoon, M; Reese, K; Schwersenski, J; Schutzman, D; Soll, R; Horbar, JD; Leahy, K; Troyer, W; Juzwicki, C; Anderson, P; Dworsky, M; Reynolds, L; Urrutia, J; Gupta, U; Adray, C

    1996-01-01

    Objective. To compare the efficacy of a synthetic surfactant (Exosurf Neonatal, Burroughs-Wellcome Co) and a modified bovine surfactant extract (Survanta, Ross Laboratories) in the treatment of neonatal respiratory distress syndrome (RDS). Design. Multicenter, randomized trial. Setting. Thirty-eight

  4. Evaluation of bovine coronavirus antibody levels, virus shedding, and respiratory disease incidence throughout the beef cattle production cycle

    Science.gov (United States)

    Objective- Determine how levels of serum antibody to bovine coronavirus (BCV) are related to virus shedding patterns and respiratory disease incidence in beef calves at various production stages. Animals- 890 crossbred beef calves from four separately managed herds at the U.S. Meat Animal Research C...

  5. Hospitalisations for respiratory syncytial virus bronchiolitis in Akershus, Norway, 1993–2000: a population-based retrospective study

    Directory of Open Access Journals (Sweden)

    Bratlid Dag

    2004-12-01

    Full Text Available Abstract Background RSV is recognized as the most important cause of serious lower respiratory tract illness in infants and young children worldwide leading to hospitalisation in a great number of cases, especially in certain high-risk groups. The aims of the present study were to identify risk groups, outcome and incidences of hospitalisation for RSV bronchiolitis in Norwegian children under two years of age and to compare the results with other studies. Methods We performed a population-based retrospective survey for the period 1993–2000 in children under two years of age hospitalised for RSV bronchiolitis. Results 822 admissions from 764 patients were identified, 93% had one hospitalisation, while 7% had two or more hospitalisations. Mean annual hospitalisation incidences were 21.7 per 1.000 children under one year of age, 6.8 per 1.000 children at 1–2 years of age and 14.1 per 1.000 children under two years of age. 77 children (85 admissions belonged to one or more high-risk groups such as preterm birth, trisomy 21 and congenital heart disease. For preterm children under one year of age, at 1–2 years of age and under two years of age hospitalisation incidences per 1.000 children were 23.5, 8.7 and 16.2 respectively. The incidence for children under two years of age with trisomy 21 was 153.8 per 1.000 children. Conclusion While the overall hospitalisation incidences and outcome of RSV bronchiolitis were in agreement with other studies, hospitalisation incidences for preterm children were lower than in many other studies. Age on admission for preterm children, when corrected for prematurity, was comparable to low-risk children. Length of hospitalisation and morbidity was high in both preterm children, children with a congenital heart disease and in children with trisomy 21, the last group being at particular high risk for severe disease.

  6. Interleukin-8,RANTES gene polymorphism and respiratory syncytial virus bronchiolitis%白介素8、RANTES基因多态性与呼吸道合胞病毒毛细支气管炎

    Institute of Scientific and Technical Information of China (English)

    田曼; 陈荣华

    2008-01-01

    呼吸道合胞病毒(respiratory syncytial virus,RSV)感染2岁以下几乎所有的儿童,但只有少数发展为比较严重的毛细支气管炎及毛细支气管炎后反复喘息.随着对其遗传学研究的不断深入,通过对RSV毛细支气管炎患儿基因型的分析,发现白介素8、RANTES存在基因多态性,且可能与RSV毛细支气管炎及毛细支气管炎后反复喘息的易感性相关.%Respiratory syncytial virus(RSV)infects nearly all children under two years old,but only minority of them developed serious bronchiolitis and subsequent wheezing.Whether there is a genetic component is not known.The common single nucleotide polymorphisms in the promoter region of interleukin-8(IL-8)and RANTES upstream of the transcription start site affect their mRNA levels and protein expressions.This review includes the new researches about the genetic association between the IL-8,RANTES gene polymorphism and RSV bronchiolitis and post-bronchiolitis wheezing.

  7. Narcissus tazetta lectin shows strong inhibitory effects against respiratory syncytial virus, influenza A (H1N1, H3N2, H5N1) and B viruses

    Indian Academy of Sciences (India)

    Linda S M Ooi; Wing-Shan Ho; Karry L K Ngai; Li Tian; Paul K S Chan; Samuel S M Sun; Vincent E C Ooi

    2010-03-01

    Amannose-binding lectin (Narcissus tazetta lectin [NTL]) with potent antiviral activity was isolated and purified from the bulbs of the Chinese daffodil Narcissus tazetta var. chinensis, using ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose, affinity chromatography on mannose–agarose and fast protein liquid chromatography (FPLC)-gel filtration on Superose 12. The purified lectin was shown to have an apparent molecular mass of 26 kDa by gel filtration and 13 kDa by SDS–PAGE, indicating that it is probably a dimer with two identical subunits. The cDNA-derived amino acid sequence of NTL as determined by molecular cloning also reveals that NTL protein contains a mature polypeptide consisting of 105 amino acids and a C-terminal peptide extension. Three-dimensional modelling study demonstrated that the NTL primary polypeptide contains three subdomains, each with a conserved mannose-binding site. It shows a high homology of about 60%–80% similarity with the existing monocot mannose-binding lectins. NTL could significantly inhibit plaque formation by the human respiratory syncytial virus (RSV) with an IC50 of 2.30 g/ml and exhibit strong antiviral properties against influenza A (H1N1, H3N2, H5N1) and influenza B viruses with IC50 values ranging from 0.20 g/ml to 1.33 g/ml in a dose-dependent manner. It is worth noting that the modes of antiviral action of NTL against RSV and influenza A virus are significantly different. NTL is effective in the inhibition of RSV during the whole viral infection cycle, but the antiviral activity of NTL is mainly expressed at the early stage of the viral cycle of influenza A (H1N1) virus. NTL with a high selective index (SI=CC50/IC50 ≥ 141) resulting from its potent antiviral activity and low cytotoxicity demonstrates a potential for biotechnological development as an antiviral agent.

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

    Directory of Open Access Journals (Sweden)

    Hubbard Gene B

    2011-01-01

    Full Text Available Abstract Background 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. Methods 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 Results 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

  9. Systemic T-helper and T-regulatory cell type cytokine responses in rhinovirus vs. respiratory syncytial virus induced early wheezing: an observational study

    Directory of Open Access Journals (Sweden)

    Vuorinen Tytti

    2009-09-01

    Full Text Available Abstract Background Rhinovirus (RV associated early wheezing has been recognized as an independent risk factor for asthma. The risk is more important than that associated with respiratory syncytial virus (RSV disease. No comparative data are available on the immune responses of these diseases. Objective To compare T-helper1 (Th1, Th2 and T-regulatory (Treg cell type cytokine responses between RV and RSV induced early wheezing. Methods Systemic Th1-type (interferon [IFN] -gamma, interleukin [IL] -2, IL-12, Th2-type (IL-4, IL-5, IL-13 and Treg-type (IL-10 cytokine responses were studied from acute and convalescence phase serum samples of sole RV (n = 23 and RSV affected hospitalized wheezing children (n = 27. The pre-defined inclusion criteria were age of 3-35 months and first or second wheezing episode. Analysis was adjusted for baseline differences. Asymptomatic children with comparable demographics (n = 11 served as controls for RV-group. Results RV-group was older and had more atopic characteristics than RSV-group. At acute phase, RV-group had higher (fold change IL-13 (39-fold, IL-12 (7.5-fold, IFN-gamma (6.0-fold and IL-5 (2.8-fold concentrations than RSV-group and higher IFN-gamma (27-fold, IL-2 (8.9-fold, IL-5 (5.6-fold and IL-10 (2.6-fold than the controls. 2-3 weeks later, RV-group had higher IFN-gamma (>100-fold, IL-13 (33-fold and IL-10 (6.5-fold concentrations than RSV-group and higher IFN-gamma (15-fold and IL-2 (9.4-fold than the controls. IL-10 levels were higher in acute phase compared to convalescence phase in both infections (p Conclusion Our results support a hypothesis that RV is likely to trigger wheezing mainly in children with a predisposition. IL-10 may have important regulatory function in acute viral wheeze.

  10. Survey of management practices related to bovine respiratory disease in preweaned calves on California dairies.

    Science.gov (United States)

    Love, W J; Lehenbauer, T W; Karle, B M; Hulbert, Lindsey E; Anderson, Randall J; Van Eenennaam, A L; Farver, T B; Aly, S S

    2016-02-01

    In the spring of 2013, a survey of California (CA) dairies was performed to characterize management practices related to bovine respiratory disease in preweaned calves, compare these practices across geographic regions of the state, and determine the principal components that explain the variability in management between herds. The questionnaire consisted of 53 questions divided into 6 sections to assess management practices affecting dairy calves from precalving to weaning. The questionnaire was mailed to 1,523 grade A licensed dairies in CA and 224 responses (14.7%) were collected. Survey response rates were similar over the 3 defined regions of CA: northern CA, northern San Joaquin Valley, and the greater southern CA region. The mean size of respondent herds was 1,423 milking cows. Most dairies reported raising preweaned calves on-site (59.7%). In 93.3% of dairies, preweaned calves were raised in some form of individual housing. Nonsaleable milk was the most frequent liquid diet fed to preweaned heifers (75.2%). Several important differences were identified between calf-raising practices in CA and practices reported in recent nationwide studies, including herd sizes, housing practices, and sources of milk fed to heifers. The differences between the CA and nationwide studies may be explained by differences in herd size. Regional differences within CA were also identified. Compared with the 2 other regions, northern CA dairies were found to have smaller herds, less Holstein cattle, calves remained with dams for longer periods of time after calving, were more likely to be certified organic dairies, and raised their own calves more often. Principal component analysis was performed and identified 11 components composed of 28 variables (questions) that explained 66.5% of the variability in the data. The identified components and questions will contribute to developing a risk assessment tool for bovine respiratory disease in preweaned dairy calves.

  11. The nasopharyngeal microbiota of feedlot cattle that develop bovine respiratory disease.

    Science.gov (United States)

    Holman, Devin B; McAllister, Tim A; Topp, Edward; Wright, André-Denis G; Alexander, Trevor W

    2015-10-22

    Bovine respiratory disease is the major cause of morbidity and mortality in feedlot cattle. The objective of this study was to compare the nasopharyngeal bacterial microbiota of healthy cattle and cattle treated for BRD in a commercial feedlot setting using a high-density 16S rRNA gene microarray (Phylochip). Samples were taken from both groups of animals (n=5) at feedlot entry (day 0) and ≥60 days after placement. Cattle diagnosed with BRD had significantly less bacterial diversity and fewer OTUs in their nasopharynx at both sampling times. The predominant phyla in both groups were Proteobacteria and Firmicutes. The relative abundance of the phylum Actinobacteria was lower in cattle treated for BRD. At the family-level there was a greater relative abundance (Pcattle compared to BRD-affected cattle. The community structure of the BRD-affected and healthy cattle were also significantly different from each other at both sampling times as measured using unweighted UniFrac distances. All entry samples of cattle diagnosed with BRD had 16S rRNA gene sequences representative of the BRD-associated bacteria Mannheimia haemolytica or Pasteurella multocida, although 3/5 healthy cattle were also positive for M. haemolytica at this time point. The results also indicate that the bovine nasopharyngeal microbiota is relatively unstable during the first 60 days in the feedlot.

  12. Immune pathogenesy of chronic obstructive pulmonary disease with respiratory syncytial virus infection%呼吸道合胞病毒感染与慢性阻塞性肺疾病发病的免疫机制

    Institute of Scientific and Technical Information of China (English)

    马冠华; 杨昆; 李敏

    2009-01-01

    慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种常见的呼吸系统疾病.随着近年来对病毒导致慢性阻塞性肺疾病急性加重(AECOPD)机制的深入研究以及呼吸道病毒检出率的提高,病毒感染在COPD发病机制中的作用受到了更多关注.呼吸道合胞病毒(respiratory syncytial vius,RSV)是常见的呼吸道病毒.有关RSV与宿主的免疫学的研究提示了COPD中RSV的易感性,可能成为某些COPD患者防治疾病发展的新方向.本文对病毒感染在AECOPD中的作用以及RSV感染与COPD发病机制的免疫研究进展现状作一综述.%Chronic obstructive pulmonary disease(COPD)is a kind of common disease in respiratory system.With the recent advances in virus-induced acute exacerbations and elevated detection rates of viruses,the etiological status of virus in COPD is getting more attention.Respiratory syncytial virus is a common respiratory virus,some researchers suggest susceptibility of RSV to COPD,which may suggest prospective prevention and therapy to certain kind of COPD patients.This article summarizes the function of virus infection in acute exacerbation COPD and makes a review of the update on the immune pathogenesy of COPD with RSV infection.

  13. Comparative analysis of Pasteurella multocida strains isolated from bovine respiratory infections.

    Science.gov (United States)

    Sellyei, Boglárka; Rónai, Zsuzsanna; Jánosi, Szilárd; Makrai, László

    2015-12-01

    Bovine respiratory disease (BRD) is the leading cause of significant economic losses in the intensive beef industry worldwide. Beside numerous risk factors Pasteurella multocida, which is regarded as a secondary pathogen, may play a role in the development of the disease. Previous studies of strains from swine pneumonia revealed that there are a few clones associated with clinical disease, suggesting that some strains may be more virulent than others. This linkage may be true in the BRD, however composition of P. multocida populations in the herds are slightly characterized. Thus, we decided to perform phenotypic and genotypic characterisation of strains isolated from calves with respiratory infection at 31 different herds in Hungary. The results demonstrated the presence of two dominant strain types. At the identical taxonomic background (P. multocida subsp. multocida) with slight phenotypic variability they could be separated by trehalose fermentation capacity, α-glucosidase activity and molecular fingerprint patterns of ERIC- and M13-PCR. Independent prevalence and geographical origin of the strain types may refer to their significance in the illness, but their comparison with strains isolated from healthy individuals is taken into consideration.

  14. Structure and functional dynamics characterization of the ion channel of the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH) transmembrane domain by combining molecular dynamics with excited normal modes.

    Science.gov (United States)

    Araujo, Gabriela C; Silva, Ricardo H T; Scott, Luis P B; Araujo, Alexandre S; Souza, Fatima P; de Oliveira, Ronaldo Junio

    2016-12-01

    The human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infection in children and elderly people worldwide. Its genome encodes 11 proteins including SH protein, whose functions are not well known. Studies show that SH protein increases RSV virulence degree and permeability to small compounds, suggesting it is involved in the formation of ion channels. The knowledge of SH structure and function is fundamental for a better understanding of its infection mechanism. The aim of this study was to model, characterize, and analyze the structural behavior of SH protein in the phospholipids bilayer environment. Molecular modeling of SH pentameric structure was performed, followed by traditional molecular dynamics (MD) simulations of the protein immersed in the lipid bilayer. Molecular dynamics with excited normal modes (MDeNM) was applied in the resulting system in order to investigate long time scale pore dynamics. MD simulations support that SH protein is stable in its pentameric form. Simulations also showed the presence of water molecules within the bilayer by density distribution, thus confirming that SH protein is a viroporin. This water transport was also observed in MDeNM studies with histidine residues of five chains (His22 and His51), playing a key role in pore permeability. The combination of traditional MD and MDeNM was a very efficient protocol to investigate functional conformational changes of transmembrane proteins that act as molecular channels. This protocol can support future investigations of drug candidates by acting on SH protein to inhibit viral infection. Graphical Abstract The ion channel of the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH) transmembrane domainᅟ.

  15. Respiratory Syncytial Virus (RSV): Treatment

    Science.gov (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  16. Associations between prior management of cattle and risk of bovine respiratory disease in feedlot cattle.

    Science.gov (United States)

    Hay, K E; Morton, J M; Schibrowski, M L; Clements, A C A; Mahony, T J; Barnes, T S

    2016-05-01

    Bovine respiratory disease (BRD) is the major cause of clinical disease and death in feedlot populations worldwide. A longitudinal study was conducted to assess associations between risk factors related to on-farm management prior to transport to the feedlot and risk of BRD in a population of feedlot beef cattle sourced from throughout the cattle producing regions of Australia. Exposure variables were derived from questionnaire data provided by farmers supplying cattle (N=10,721) that were a subset of the population included in a nationwide prospective study investigating numerous putative risk factors for BRD. Causal diagrams were used to inform model building to allow estimation of effects of interest. Multilevel mixed effects logistic regression models were fitted within the Bayesian framework. Animals that were yard weaned were at reduced risk (OR: 0.7, 95% credible interval: 0.5-1.0) of BRD at the feedlot compared to animals immediately returned to pasture after weaning. Animals that had previously been fed grain (OR: 0.6, 95% credible interval: 0.3-1.1) were probably at reduced risk of BRD at the feedlot compared to animals not previously fed grain. Animals that received prior vaccinations against Bovine viral diarrhoea virus 1 (OR: 0.8, 95% credible interval: 0.5-1.1) or Mannheimia haemolytica (OR: 0.8, 95% credible interval: 0.6-1.0) were also probably at reduced risk compared to non-vaccinated animals. The results of this study confirm that on-farm management before feedlot entry can alter risk of BRD after beef cattle enter feedlots.

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

    Science.gov (United States)

    2013-01-01

    Naval Medical Research Unit 3, 1209 Payne Ave, Austin, TX 78757 (emily.rowlinson@gmail.com). The Journal of Infectious Diseases 2013;208(S3):S189–96...Damanhour by combining population-based surveillance data with healthcare utilization patterns. In addition to a sub- stantial burden of pediatric ...syncytial virus infection in tropical and developing countries. Trop Med Int Health 1998; 3:268–80. 2. Nair H, Nokes DJ, Gessner BD, et al. Global

  18. Laboratory test descriptions for bovine respiratory disease diagnosis and their strengths and weaknesses: Gold standards for diagnosis, do they exist?

    OpenAIRE

    Fulton, Robert W.; Confer, Anthony W.

    2012-01-01

    The diagnosis of bovine respiratory diseases (BRD) poses significant challenges to the clinician as there are numerous infectious etiologies, operating singly or most often in combination. Clinical signs alone may not be diagnostic and the diagnostic laboratory is often used to assist the clinician. Recently many molecular-based tests have been taken from the research laboratory to the veterinary diagnostic laboratory. This review describes the “traditional tests” and several “molecular tests...

  19. 特异性免疫在呼吸道合胞病毒疫苗增强疾病过程中的作用%The function of adaptive immunity in respiratory syncytial virus vaccine-ehanced disease

    Institute of Scientific and Technical Information of China (English)

    胡勇; 钱景

    2011-01-01

    呼吸道合胞病毒(RSV)疫苗可诱发疫苗增强疾病,以肺组织广泛的炎细胞浸润和嗜酸性粒细胞增多为典型特征.探索RSV疫苗增强疾病的免疫机制,尤其是宿主体液和细胞免疫反应不平衡在疫苗增强疾病过程中的作用,有助于安全有效的RSV疫苗的研究.%Respiratory syncytial virus(RSV) vaccine induced vaccine-enhanced disease, was manifested typically as lung inflammatory cell infiltration and eosinophilia extensively. The study on the immune mechanism, especially the unbalance response of host humoral and cellular immunity, is helpful for the development of safe and effective vaccine for RSV.

  20. Discovery of β-D-2'-deoxy-2'-α-fluoro-4'-α-cyano-5-aza-7,9-dideaza adenosine as a potent nucleoside inhibitor of respiratory syncytial virus with excellent selectivity over mitochondrial RNA and DNA polymerases.

    Science.gov (United States)

    Clarke, Michael O; Mackman, Richard; Byun, Daniel; Hui, Hon; Barauskas, Ona; Birkus, Gabriel; Chun, Byoung-Kwon; Doerffler, Edward; Feng, Joy; Karki, Kapil; Lee, Gary; Perron, Michel; Siegel, Dustin; Swaminathan, Swami; Lee, William

    2015-06-15

    Novel 4'-substituted β-d-2'-deoxy-2'-α-fluoro (2'd2'F) nucleoside inhibitors of respiratory syncytial virus (RSV) are reported. The introduction of 4'-substitution onto 2'd2'F nucleoside analogs resulted in compounds demonstrating potent cell based RSV inhibition, improved inhibition of the RSV polymerase by the nucleoside triphosphate metabolites, and enhanced selectivity over incorporation by mitochondrial RNA and DNA polymerases. Selectivity over the mitochondrial polymerases was found to be extremely sensitive to the specific 4'-substitution and not readily predictable. Combining the most potent and selective 4'-groups from N-nucleoside analogs onto a 2'd2'F C-nucleoside analog resulted in the identification of β-D-2'-deoxy-2'-α-fluoro-4'-α-cyano-5-aza-7,9-dideaza adenosine as a promising nucleoside lead for RSV.

  1. Sensitivites in vitro to antimicrobial drugs of bovine mycoplasmas isolated from respiratory and genital tracts.

    Science.gov (United States)

    Kishima, M; Hashimoto, K; Minato, H

    1978-01-01

    A total of 155 Mycoplasma strains were examined for sensitivity to nine antibiotics and four nitrofurans by the agar dilution method. They consisted of 69 strains of Mycoplasma bovirhinis, 33 strains of M. bovigenitalium, 49 strains of Acholeplasma laidlawii and four strains of A. modicum isolated from the nasal secretions, tracheas and lungs of calves manifesting respiratory symptoms and from bovine genital tracts collected at a slaughterhouse. As a result, furamizole and mitomycin C showed the strongest growth-inhibiting effect on all the strains. They were followed in this effect by kitasamycin tartrate, spiramycin adipate, tylosin tartrate, tetracycline-HCl and chloramphenicol. Furthermore, these five drugs were followed in the effect by furazolidone, nitrofurantoin and sodium nifurstyrenate. Fradiomycin sulfate and kanamycin sulfate showed only little effect on all the strains. Erythromycin lactobionate showed a strong growth-inhibiting effect on the Acholeplasma strains, but not on the Mycoplasma strains. There were some cross resistant strains of the Acholeplasma species to the effects of the macrolides.

  2. Modern Approach to the Enigma of Bovine Respiratory Disease Complex: A Review

    Directory of Open Access Journals (Sweden)

    Vladimir S. Kurćubić

    2014-01-01

    Full Text Available Research on Bovine Respiratory Disease Complex (BRDC has strongly contributed to a better understanding of disease at both global and local levels. New agents have been identified and their nature has been better known since then, as well as all the factors that predispone the development of BRDC. Serious work in a number of researches has led to results that have proven significant synergistic interactions between viruses and bacteria that lead to the BRDC and complicate the prevention and treatment of the diseased cattle. Nowadays, it is necessary to apply the latest molecular and other techniques in order to examine in detail all of the specific causes, describe them accurately and provide effective prevention. This can primarily be accomplished by producing different types of vaccines, which are to be improved constantly. Serious progress has been made in researches on immunogenic properties and antimicrobial activity of various natural and synthetic substances in order to improve the production of more effective vaccines for control, as well as the development of a new generation of antibiotics to treat the disease. BRDC prevention programs have been successful, in which great importance was given to proper vaccinations and herd management practices. BRDC is still the most important disease of cattle from an economic point of view, since it causes great losses and expenses.

  3. 呼吸道合胞病毒毛细支气管炎患儿IL-17改变的意义%Changes of serum IL-17 level in infants with respiratory syncytial virus bronchiolitis

    Institute of Scientific and Technical Information of China (English)

    王同友; 王红兵

    2012-01-01

    目的 探讨呼吸道合胞病毒(RSV)感染毛细支气管炎患儿IL-17改变的意义.方法 采用ELISA方法检测30例RSV感染毛细支气管炎患儿(RSV毛支组)、30例非RSV感染支气管肺炎患儿(非RSV肺炎组)以及 25例健康对照儿(对照组)血清中IL-17浓度,并进行比较分析.结果 RSV毛支组患儿血清IL-17水平明显高于其他2组(P<0.01);非RSV肺炎组患儿血清IL-17水平高于对照组(P<0.01).结论 小儿呼吸道合胞病毒性毛细支气管炎的发生和发展与IL-17异常表达有关.%Objective To explore the change of interleukin 17 (IL -17) in infants with respiratory syncytial virus bronchiolitis and their clinical significance . Methods Serum IL — 17 of 30 respiratory syncytial virus ( RSV) bronchioli— tis infants, 30 pneumonia infants without RSV infection and 25 health controls were detected by using ELISA method. Results Level of serum IL -17 were obviously higher in RSV bronchiolitis infants than those in pneumonia infants with -out RSV infection and health controls (P <0.01). Level of serum IL — 17 of pneumonia infants without RSV was obvi — ously high compared with normal group (P <0.01). Conclusion IL -17 may play an important role in the pathogene-sis of RSV Bronchiolitis in infant.

  4. Neutrophil activation and protease imbalance in respiratory tract of infants with respiratory syncytial virus bronchiolitis%呼吸道合胞病毒毛细支气管炎患儿中性粒细胞活化及蛋白酶平衡的研究

    Institute of Scientific and Technical Information of China (English)

    刘金玲; 陈志敏

    2009-01-01

    Objective To better understand the neutrophil activation and protease imbalance in respiratory syncytial virus (RSV) bronchiolitis. Methods Pediatric patients with RSV bronchiolitis were collected,11 with the Lowell scores ≥ 10 (severe group),and 19 with the Lowell scores 0.05).结论 呼吸道合胞病毒毛支气道局部存在大量中性粒细胞聚集活化和蛋白酶系统失衡,并可能在其发病中起重要作用.

  5. Fine mapping of Loci on BTA2 and BTA26 Associated with Bovine Viral Diarrhea Persistent Infection and Linked with Bovine Respiratory Disease in Cattle

    Directory of Open Access Journals (Sweden)

    Ricardo eZanella

    2011-11-01

    Full Text Available Bovine respiratory disease (BRD is considered to be the most costly infectious disease in the cattle industry. Bovine viral diarrhea virus (BVDV is one of the pathogens involved with the BRD complex of disease. Bovine viral diarrhea virus infection also negatively impacts cow reproduction and calf performance. Loci associated with persistently infected animals (BVD-PI and linked with BRD have previously been identified near 14 Mb on bovine chromosome 2 (BTA2 and 15.3 Mb on bovine chromosome 26 (BTA26. The objective of this study was to refine the loci associated with BVD-PIand linked with BRD. Association testing for BVD-PI was performed on a population of 65 BVD-PI calves, 51 of their dams, and 60 unaffected calves (controls with 175 single nucleotide polymorphisms (SNPs on BTA2 and 209 SNPs on BTA26. Comparisons were made between BVD-PI calves and controls calves and the dams of BVD-PI calves and controls calves. For the linkage analysis of BRD, the same markers were used to genotype 2 half sib-families consisting of the sires and 72 BRD positive and 148 BRD negative offspring. Using an allelic chi-square test, 11 loci on BTA2 and 8 loci on BTA26 were associated with the dams of the BVD-PI calves (P < 0.05 and 5 loci on BTA2 and 10 loci on BTA26 were associated with BVD-PI calves. One locus on BTA2 and two loci on BTA26 were found to be linked (P < 0.05 with BRD. These results further refined the loci associated and linked with BVD-PI and BRD, respectively.

  6. Associations between feedlot management practices and bovine respiratory disease in Australian feedlot cattle.

    Science.gov (United States)

    Hay, K E; Morton, J M; Clements, A C A; Mahony, T J; Barnes, T S

    2016-06-01

    Bovine respiratory disease (BRD) is the major cause of clinical disease and death in feedlot cattle. A prospective longitudinal study was conducted in a population of Australian feedlot cattle to assess associations between factors related to feedlot management and risk of BRD. In total, 35,131 animals in 170 pens (cohorts) inducted into 14 feedlots were included in statistical analyses. Causal diagrams were used to inform model building to allow separate estimation of total and direct effects. Multilevel mixed effects logistic regression models were fitted within the Bayesian framework. The placement of pen water troughs such that they could be accessed by animals in adjoining pens was associated with markedly increased risk of BRD (OR 4.3, 95% credible interval: 1.4-10.3). Adding animals to pens over multiple days was associated with increased risk of BRD across all animals in those pens compared to placing all animals in the pen on a single day (total effect: OR 1.9, 95% credible interval: 1.2-2.8). The much attenuated direct effect indicated that this was primarily mediated via factors on indirect pathways so it may be possible to ameliorate the adverse effects of adding animals to pens over multiple days by altering exposure to these intervening factors (e.g. mixing history). In pens in which animals were added to the pen over multiple days, animals added ≥7 days (OR: 0.7, credible interval: 0.5-0.9) or 1-6 days (OR: 0.8, credible interval: 0.7-1.0) before the last animal was added were at modestly reduced risk of BRD compared to the animals that were added to the pen on the latest day. Further research is required to disentangle effects of cohort formation patterns at animal-level and higher levels on animal-level risk of BRD. Vaccination against Bovine herpesvirus 1 at feedlot entry was investigated but results were inconclusive and further research is required to evaluate vaccine efficacy. We conclude that there are practical interventions available to

  7. Associations between animal characteristic and environmental risk factors and bovine respiratory disease in Australian feedlot cattle.

    Science.gov (United States)

    Hay, K E; Morton, J M; Mahony, T J; Clements, A C A; Barnes, T S

    2016-03-01

    A prospective longitudinal study was conducted in a population of Australian feedlot cattle to assess associations between animal characteristic and environmental risk factors and risk of bovine respiratory disease (BRD). Animal characteristics were recorded at induction, when animals were individually identified and enrolled into study cohorts (comprising animals in a feedlot pen). Environmental risk factors included the year and season of induction, source region and feedlot region and summary variables describing weather during the first week of follow-up. In total, 35,131 animals inducted into 170 cohorts within 14 feedlots were included in statistical analyses. Causal diagrams were used to inform model building and multilevel mixed effects logistic regression models were fitted within the Bayesian framework. Breed, induction weight and season of induction were significantly and strongly associated with risk of BRD. Compared to Angus cattle, Herefords were at markedly increased risk (OR: 2.0, 95% credible interval: 1.5-2.6) and tropically adapted breeds and their crosses were at markedly reduced risk (OR: 0.5, 95% credible interval: 0.3-0.7) of developing BRD. Risk of BRD declined with increased induction weight, with cattle in the heaviest weight category (≥480kg) at moderately reduced risk compared to cattle weighing risk compared to animals inducted during spring. Knowledge of these risk factors may be useful in predicting BRD risk for incoming groups of cattle in Australian feedlots. This would then provide the opportunity for feedlot managers to tailor management strategies for specific subsets of animals according to predicted BRD risk.

  8. Effect of bovine respiratory disease and overall pathogenic disease incidence on carcass traits.

    Science.gov (United States)

    Garcia, M D; Thallman, R M; Wheeler, T L; Shackelford, S D; Casas, E

    2010-02-01

    The objective this study was to evaluate the effects of incidence of bovine respiratory disease (BRD) and overall incidence of pathogenic diseases (IPD) on carcass traits. Two independent populations were used. The first population included crossbred steers (GPE7; n = 642) derived from sires of 7 Bos taurus breeds: Angus, Charolais, Gelbvieh, Hereford, Limousin, Red Angus, and Simmental. The second population included crossbred steers (GPE8; n = 621) derived from tropically adapted Bos taurus breeds and Bos indicus-influenced breeds: Beefmaster, Brangus, Bonsmara, and Romosinuano, as well as Hereford and Angus. Treatment records for BRD, infectious keratoconjunctivitis, and infectious pododermatitis were available for these populations. Incidence of BRD was treated as an independent effect. Incidences of the 3 microbial pathogenic diseases were pooled into a single trait to represent overall pathogenic disease incidence. Traits evaluated were HCW; KPH; LM area; marbling score; fat thickness; dressing percentage; yield grade; retail, fat, and bone yields; and meat tenderness. Both BRD and IPD were associated with differences in yield grade in GPE7 and GPE8 steers. Animals treated for BRD had decreased yield grades (P = 0.003 and P = 0.02, in GPE7 and GPE8, respectively) compared with untreated animals. Animals treated for IPD had decreased yield grades (P = 0.0006 and P = 0.004, in GPE7 and GPE8, respectively) compared with untreated animals. Incidence of BRD and IPD were associated with a reduction in fat thickness in GPE7 and GPE8 steers. Animals treated for BRD had reduced adjusted fat measurements (P = 0.0007 and P = 0.01, in GPE7 and GPE8) compared with untreated animals. Animals treated for IPD also had reduced adjusted fat measurements (P = 0.0003 and P = 0.002, in GPE7 and GPE8) compared with untreated animals. Animals treated for BRD (P carcass traits should be given consideration by future studies that aim to develop selection strategies based on specific

  9. Investigation of polymerase chain reaction assays to improve detection of bacterial involvement in bovine respiratory disease.

    Science.gov (United States)

    Bell, Colin J; Blackburn, Paul; Elliott, Mark; Patterson, Tony I A P; Ellison, Sean; Lahuerta-Marin, Angela; Ball, Hywel J

    2014-09-01

    Bovine respiratory disease (BRD) causes severe economic losses to the cattle farming industry worldwide. The major bacterial organisms contributing to the BRD complex are Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, Pasteurella multocida, and Trueperella pyogenes. The postmortem detection of these organisms in pneumonic lung tissue is generally conducted using standard culture-based techniques where the presence of therapeutic antibiotics in the tissue can inhibit bacterial isolation. In the current study, conventional and real-time polymerase chain reaction (PCR) assays were used to assess the prevalence of these 5 organisms in grossly pneumonic lung samples from 150 animals submitted for postmortem examination, and the results were compared with those obtained using culture techniques. Mannheimia haemolytica was detected in 51 cases (34%) by PCR and in 33 cases (22%) by culture, H. somni was detected in 35 cases (23.3%) by PCR and in 6 cases (4%) by culture, Myc. bovis was detected in 53 cases (35.3%) by PCR and in 29 cases (19.3%) by culture, P. multocida was detected in 50 cases (33.3%) by PCR and in 31 cases (20.7%) by culture, and T. pyogenes was detected in 42 cases (28%) by PCR and in 31 cases (20.7%) by culture, with all differences being statistically significant. The PCR assays indicated positive results for 111 cases (74%) whereas 82 cases (54.6%) were culture positive. The PCR assays have demonstrated a significantly higher rate of detection of all 5 organisms in cases of pneumonia in cattle in Northern Ireland than was detected by current standard procedures.

  10. A literature review of antimicrobial resistance in Pathogens associated with bovine respiratory disease.

    Science.gov (United States)

    DeDonder, K D; Apley, M D

    2015-12-01

    The objective of this paper was to perform a critical review of the literature as it pertains to the current status of antimicrobial resistance in pathogens associated with bovine respiratory disease (BRD) in beef cattle and to provide a concise yet informative narrative on the most relevant publications available. As such, the scientific literature contained in PubMed, AGRICOLA, and CAB were searched in February of 2014 for articles related to susceptibility testing of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni from cases of BRD. Titles and abstracts were read and 105 articles that were relevant to the subject of BRD antibiotic resistance were attained for further review. After the application of exclusion criterion (publications must have originated from North America, be in English, adhere to standards set forth by the Clinical and Laboratory Standards Institute, and be concerning antimicrobial resistance in BRD in beef cattle), 16 articles remained and are the focus of this publication. Due to the disparate data from the few studies that investigate susceptibility testing of BRD pathogens, a quantitative assessment or meta-analysis was not performed on the studies presented in this review. However, considering diagnostic lab data, there appears to be a clear trend of a decrease in susceptibility of the three major BRD pathogens to the antimicrobials used commonly for treatment and control of BRD. Studies performing sensitivity testing on healthy cattle report much lower resistance, but it remains unclear if this is because of a true lack of resistance mechanisms, or if the isolates do contain quiescent genes for resistance that are only phenotypically expressed following the administration of an antimicrobial for either treatment or control of BRD. Future research to address this question of genotype and phenotypic expression before and after antimicrobial administration will further advance our knowledge in this area.

  11. Characterization of Mannheimia haemolytica isolated from feedlot cattle that were healthy or treated for bovine respiratory disease.

    Science.gov (United States)

    Klima, Cassidy L; Alexander, Trevor W; Hendrick, Steve; McAllister, Tim A

    2014-01-01

    Mannheimia haemolytica is the principal bacterial pathogen associated with bovine respiratory disease (BRD). As an opportunistic pathogen, M. haemolytica is also frequently isolated from the respiratory tract of healthy cattle. This study examined the characteristics of M. haemolytica collected using deep nasal swabs from healthy cattle (n = 49) and cattle diagnosed with BRD (n = 41). Isolates were analyzed by pulsed-field gel electrophoresis (PFGE), serotyped, and tested for antimicrobial susceptibility. Polymerase chain reaction (PCR) was used to screen isolates for virulence [leukotoxin C (lktC), putative adhesin (ahs), outer-membrane lipoprotein (gs60), O-sialoglycoprotease (gcp), transferring-binding protein B (tbpB) and UDP-N-acetyl-D-glucosamine-2-epimerase (nmaA)] and antimicrobial resistance [tet(H), bla ROB-1, erm(X), erm(42), msr(E)-mph(E) and aphA-1] genes. Isolates were genetically diverse but in three instances, M. haemolytica with the same pulsotype, resistance phenotype, and genotype were collected from cattle with BRD. This occurred once between cattle located in two different feedlots, once between cattle in the same feedlot, but in different pens, and once among cattle from the same feedlot in the same pen. Isolates from healthy cattle were primarily serotype 2 (75.5%) while those from individuals with BRD were serotype 1 (70.7%) or 6 (19.5%). Resistance to at least one antibiotic occurred more frequently (P bovine respiratory disease in western Canadian feedlots.

  12. Bronchiolitis, respiratory syncytial virus, and recurrent wheezing: what is the relationship? A bronquiolite pelo virus sincicial respiratório e o chiado recorrente: qual a relação?

    Directory of Open Access Journals (Sweden)

    Claudia de Brito Fonseca

    2003-01-01

    Full Text Available Various follow-up studies of children hospitalized with bronchiolitis caused by respiratory syncytial virus have demonstrated that a significant proportion of infants (50% have recurrent wheezing during childhood. Nevertheless, the relationship between these two entities, if any, has not been established. In order to explain this observation, several hypotheses have been proposed. The first suggests that some children could have an individual predisposition to bronchiolitis caused by respiratory syncytial virus and recurrent wheezing. The virus could be a marker of this condition, and the individual predisposition could in turn be related to an individual hypersensitivity to common allergens (atopy, airway hyperreactivity, or to some disorder related to pulmonary anatomy or physiology that was present before the acute episode of bronchiolitis. Another hypothesis proposes that respiratory syncytial virus could be directly responsible for recurrent wheezing. During an episode of bronchiolitis, the damage in the airway mucosa caused by the vital inflammatory response to infection contributes to sensitivity to other allergens or exposes irritant receptors, resulting in recurrent wheezing. For this review, we analyzed the studies that discuss these hypotheses with the purpose of clarifying the mechanisms for the important issue of recurrent wheezing in childhood.Os diversos estudos de seguimento de crianças hospitalizadas por bronquiolite pelo virus sincicial respiratório demonstram, em média, 50% de chance de evoluir com novos episódios de chiado no peito. Apesar desta constatação, não foi estabelecida a relação entre a bronquiolite pelo virus sincicial respiratório e a recorrência dos episódios de chiado. A primeira hipótese é de que o indivíduo poderia ter uma predisposição para a repetição do quadro de chiado e também para a própria bronquiolite como manifestação da infecção pelo virus sincicial respiratório. O v

  13. A mixed treatment meta-analysis of antibiotic treatment options for bovine respiratory disease - An update.

    Science.gov (United States)

    O'Connor, A M; Yuan, C; Cullen, J N; Coetzee, J F; da Silva, N; Wang, C

    2016-09-15

    Bovine respiratory disease is the most economically important disease of feedlot cattle in North America. Choice of antibiotic is a critical factor for producers and veterinarians. We previously published a mixed-treatment comparison meta-analysis that combined evidence from published trials and published estimates of comparative efficacy for 12 antibiotics registered for use in the USA. Some of the comparative efficacy estimates were based only on indirect evidence. Since the original review was published, new studies that provide direct evidence of comparative efficacy have been published. We updated the original review to include the current evidence. We also compared the results from the indirect estimates from the prior model with the observed results from randomized control trials. We repeated the original search and found that five of the new studies met the criteria for inclusion in the updated review. Four of these studies provided new data on direct comparisons of active drugs. The results from one study (performed in 2002) that compared ceftiofur pinna and enrofloxacin were inconsistent with the network and were excluded from the analysis. Three new direct comparison studies examined gamithromycin compared with tulathromycin, florfenicol, and tilmicosin. The results of our analysis suggested that the indirect estimates from the prior model provided reasonable estimates of the risk ratios revealed by the primary studies. For example, for the comparison of gamithromycin (referent) with tulathromycin, the original model predicted a risk ratio of re-treatment of 0.54 (95% credible interval 0.27-0.87). The subsequent randomized controlled trial revealed that the observed risk ratio of re-treatment was 0.59 (95% confidence interval 0.45-0.78). The results of other comparisons were also similar. For the gamithromycin (referent) to florfenicol comparison, the observed randomized trial RR was 1.17 (95% confidence interval 0.83-1.64) and the indirect estimate of

  14. Diagnosis of a mixed mycoplasma infection associated with a severe outbreak of bovine pinkeye in young calves.

    Science.gov (United States)

    Levisohn, Sharon; Garazi, Shlomo; Gerchman, Irinna; Brenner, Jacob

    2004-11-01

    Mycoplasma bovoculi and Mycoplasma bovis were both isolated from conjunctival swabs taken from young calves showing symptoms consistent with infectious bovine keratoconjunctivitis (pinkeye). No Moraxella spp. or other nonmycoplasma bacteria were isolated in association with this severe clinical outbreak. Based on laboratory tests and clinical observations, the first phase of the disease was likely pneumonic in nature, possibly caused by bovine respiratory syncytial virus and M. bovis. In the subsequent phase of the disease course, infection with both M. bovoculi and M. bovis resulted in ocular disease. A combination of microbiological, serological, and molecular diagnosticmethods was used to elucidate the etiology of the outbreak.

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

    Science.gov (United States)

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

    2015-01-01

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

  16. B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model.

    Science.gov (United States)

    Dunussi-Joannopoulos, Kyri; Hancock, Gerald E; Kunz, Arthur; Hegen, Martin; Zhou, Xiaochuan X; Sheppard, Barbara J; Lamothe, Jennifer; Li, Evelyn; Ma, Hak-Ling; Hamann, Philip R; Damle, Nitin K; Collins, Mary

    2005-10-01

    We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.

  17. The ectodomains but not the transmembrane domains of the fusion proteins of subtypes A and B avian pneumovirus are conserved to a similar extent as those of human respiratory syncytial virus.

    Science.gov (United States)

    Naylor, C J; Britton, P; Cavanagh, D

    1998-06-01

    The fusion glycoprotein (F(B)) gene of five strains of the B subtype of avian pneumovirus (APV; turkey rhinotracheitis virus) has been sequenced. The length of the F(B) protein was 538 amino acids, identical to that of the F protein of subtype A virus, with which it had 74% and 83% overall nucleotide and deduced amino acid identities, respectively. The F(B) and F(A) ectodomains had 90% amino acid identity, very similar to the 91% identity between the ectodomains of the F proteins of subtype A and B human respiratory syncytial virus (HRSV). As with HRSV, the F2 polypeptide was less conserved (83% identity) than F1 (94%). In contrast to the ectodomain, the transmembrane and cytoplasmic domains of the two APV subtypes were much less conserved (30% and 48% identity, respectively) than those of HRSV (92% and 87%, respectively). Comparisons within all the genera of the Paramyxoviridae (Pneumovirus, Morbillivirus, Paramyxovirus and Rubullavirus) show that low amino acid identity between F protein transmembrane domains is a feature of different species of virus rather than of strain differences. This may indicate that the two subtypes of APV have evolved in different geographical regions and/or different avian species. This is the first report of an F gene sequence from a subtype B APV.

  18. Bayesian estimation of the accuracy of the calf respiratory scoring chart and ultrasonography for the diagnosis of bovine respiratory disease in pre-weaned dairy calves.

    Science.gov (United States)

    Buczinski, Sébastien; L Ollivett, Terri; Dendukuri, Nandini

    2015-05-01

    There is currently no gold standard method for the diagnosis of bovine respiratory disease (BRD) complex in Holstein pre-weaned dairy calves. Systematic thoracic ultrasonography (TUS) has been used as a proxy for BRD, but cannot be directly used by producers. The Wisconsin calf respiratory scoring chart (CRSC) is a simpler alternative, but with unknown accuracy. Our objective was to estimate the accuracy of CRSC, while adjusting for the lack of a gold standard. Two cross sectional study populations with a high BRD prevalence (n=106 pre-weaned Holstein calves) and an average BRD prevalence (n=85 pre-weaned Holstein calves) from North America were studied. All calves were simultaneously assessed using CRSC (cutoff used ≥ 5) and TUS (cutoff used ≥ 1cm of lung consolidation). Bayesian latent class models allowing for conditional dependence were used with informative priors for BRD prevalence and TUS accuracy (sensitivity (Se) and specificity (Sp)) and non-informative priors for CRSC accuracies. Robustness of the model was tested by relaxing priors for prevalence or TUS accuracy. The SeCRSC (95% credible interval (CI)) and SpCRSC were 62.4% (47.9-75.8) and 74.1% (64.9-82.8) respectively. The SeTUS was 79.4% (66.4-90.9) and SpTUS was 93.9% (88.0-97.6). The imperfect accuracy of CRSC and TUS should be taken into account when using those tools to assess BRD status.

  19. Risk factors for acute respiratory syncytial virus infection of lower respiratory tract in hospitalized infants%婴儿急性下呼吸道呼吸道合胞病毒感染的危险因素研究

    Institute of Scientific and Technical Information of China (English)

    张晓波; 刘丽娟; 施鹏; 蒋高立; 贾品; 王传凯; 王立波; 钱莉玲

    2014-01-01

    染的风险大为增加.%Objective 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).Method ALRI infants admitted to Children's Hospital of Fudan University from March 1 st,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.Result Among 1 726 ALRI infants,there were 913 RSV-positive infants (52.9%).The occurrence of RSV infection had a seasonal variation,with a peak in winter (59.1%).The median (P25,P75) age of RSV infants was 64 (21-155) days.The gestational age (GA) and body weight (BW) was (37.5 ± 2.4) weeks and (3.07 ±0.66) kg,respectively.The male/female ratio among these was 1.9:1.RSV infection was more popular among infants in the families with smoking members,crowded living conditions,history of atopic mother.Differences of the proportion of patients with underlying disease between RSV-positive and negative groups were statistically significant (59.4% vs.54.2%,P < 0.05).Univariate logistic regression demonstrated that factors increasing the risk of RSV infection were:GA < 37weeks (OR =1.346,95% CI:1.037-1.748),birth weight < 2 500 g (OR =1.447,95 % CI:1.103-1.898),underlying diseases (OR =1.232,95 % CI:1.018-1.492),underlying CHD (OR =1.391,95% CI:1.120-1.728),environmental tobacco smoke exposure (OR =1.254,95% CI:1.035-1.519),mother with atopic diseases (OR =1.827,95% CI:1.296-2.573),crowded house with four or

  20. In vitro sensitivities to antimicrobial drugs of ureaplasmas isolated from the bovine respiratory tract, genital tract and eye.

    Science.gov (United States)

    Kishima, M; Hashimoto, K

    1979-09-01

    The sensitivity to 18 antimicrobial drugs was examined for 66 strains of Ureaplasma sp isolated from respiratory tracts of calves suffering from enzootic pneumonia, urinary tracts of bulls and eyes of cows suffering from infectious bovine kerato-conjunctivitis. Furamizole, tiamulin fumarate, erythromycin lactobionate, malidomycin C, doxycycline hydrochloride, kitasamycin tartrate, tylosin tartrate, T-2636C, tetracycline hydrochloride, oxytetracycline hydrochloride, chlortetracycline hydrochloride, oleandomycin phosphate, furazolidone, spiramycin adipate, chloramphenicol and thiophenicol showed strong inhibiting activity on all the test strains. Among them, furamizole, tiamulin fumarate and erythromycin lactobionate were most active. Kanamycin sulphate showed weak activity on all the strains tested. The differences in origin of the test strains did not affect their sensitivity to any of the drugs.

  1. Laboratory test descriptions for bovine respiratory disease diagnosis and their strengths and weaknesses: gold standards for diagnosis, do they exist?

    Science.gov (United States)

    Fulton, Robert W; Confer, Anthony W

    2012-07-01

    The diagnosis of bovine respiratory diseases (BRD) poses significant challenges to the clinician as there are numerous infectious etiologies, operating singly or most often in combination. Clinical signs alone may not be diagnostic and the diagnostic laboratory is often used to assist the clinician. Recently many molecular-based tests have been taken from the research laboratory to the veterinary diagnostic laboratory. This review describes the "traditional tests" and several "molecular tests" and discusses the benefits and limitations of the tests and their interpretation. Clinicians should consult with their diagnostic laboratory regarding the interpretation of the test results. The rate of development and use of molecular diagnostic tests have outpaced validation, standardization, and standards for interpretation relative to their use in BRD diagnostics.

  2. Comparison of genotypic and phenotypic characterization methods for Pasteurella multocida isolates from fatal cases of bovine respiratory disease.

    Science.gov (United States)

    Taylor, Jared D; Fulton, Robert W; Dabo, S Mady; Lehenbauer, Terry W; Confer, Anthony W

    2010-05-01

    Bovine respiratory disease (BRD) is the most costly disease of beef cattle in North America. Because Pasteurella multocida is a commensal of the upper respiratory tract, it is generally considered an opportunistic pathogen. However, studies in swine indicated that there may be a limited number of strains associated with disease, suggesting that some are more virulent than others. Although this may also be true of isolates from cattle, appropriate typing methods must be established before this possibility can be investigated. The purpose of this study was to compare effectiveness of polymerase chain reaction (PCR) fingerprinting to more traditional approaches for typing bovine P. multocida isolates. Isolates were obtained from 41 cases of fatal BRD and subjected to random amplified polymorphic DNA PCR (RAPD-PCR), whole cell protein (WCP) profiles, outer membrane protein (OMP) profiles, and serotyping. The discrimination index was calculated for each typing method and combinations of each using Simpson's index of diversity. Correlation coefficients were calculated to assess concordance between classification results achieved through genotypic (RAPD-PCR) and phenotypic (WCP, OMP, and serotyping) approaches. All characterization methods were capable of discriminating between isolates. However, there was poor concordance between techniques. There were also few significant associations between typing results and epidemiologic data. Random amplified polymorphic DNA PCR was validated as being a repeatable and reliable means of discriminating between P. multocida isolates obtained from cattle. Isolates obtained from fatal cases of BRD in calves in a commercial feedlot demonstrated significant diversity, justifying additional investigation into whether P. multocida is a strictly opportunistic pathogen in cattle.

  3. Alimentary and respiratory tract lesions in eight medically fragile Holstein cattle with bovine leukocyte adhesion deficiency (BLAD).

    Science.gov (United States)

    Ackermann, M R; Kehrli, M E; Laufer, J A; Nusz, L T

    1996-05-01

    Lesions in the alimentary tract were studied in eight medically fragile Holstein cattle homozygous for the bovine leukocyte adhesion deficiency (BLAD) allele as determined by polymerase chain reaction and restriction endonuclease analysis. These cattle received institutional medical care but died or were euthanatized because of chronic debilitation associated with diarrhea (6/8) and pneumonia (4/8). The six cattle with diarrhea had acute (n = 3) or chronic (n = 3) intestinal ulcers, but the other two remained relatively healthy for 3 years and did not develop intestinal tract ulcers. Ulcerated areas were present in the small intestine in six animals, and two of these also had ulcers in the large intestine. Ulcers were covered by thick exudates that, in chronic lesions, partially occluded the intestinal lumen. Intramural and serosal fibrosis also contributed to lumen constriction. Pseudomonas aeruginosa was isolated from the intestine of four cattle. Bovine viral disease virus and Salmonella were not isolated from the five cattle that were tested. Respiratory tract lesions consisted of dense infiltrates of neutrophils in bronchi, bronchioles, and alveoli. This study suggests that intestinal lesions are integral to the demise of BLAD cattle that receive intensive medical care and that neutrophils do infiltrate the lung and enter airway lumina, despite the adhesion deficiency.

  4. Comparative analysis of replication characteristics of BoHV-1 subtypes in bovine respiratory and genital mucosa explants: a phylogenetic enlightenment

    Directory of Open Access Journals (Sweden)

    Steukers Lennert

    2011-02-01

    Full Text Available Abstract In general, members of the Alphaherpesvirinae use the epithelium of the upper respiratory and/or genital tract as a preferential site for primary replication. Bovine herpesvirus type 1 (BoHV-1 may replicate at both sites and cause two major clinical entities designated as infectious bovine rhinotracheitis (IBR and infectious pustular vulvovaginitis/balanoposthitis (IPV/IPB in cattle. It has been hypothesized that subtype 1.1 invades preferentially the upper respiratory mucosa whereas subtype 1.2 favors replication at the peripheral genital tract. However, some studies are in contrast with this hypothesis. A thorough study of primary replication at both mucosae could elucidate whether or not different BoHV-1 subtypes show differences in mucosa tropism. We established bovine respiratory and genital organ cultures with emphasis on maintenance of tissue morphology and viability during in vitro culture. In a next step, bovine respiratory and genital mucosa explants of the same animals were inoculated with several BoHV-1 subtypes. A quantitative analysis of viral invasion in the mucosa was performed at 0 h, 24 h, 48 h and 72 h post inoculation (pi by measuring plaque latitude and penetration depth underneath the basement membrane. All BoHV-1 subtypes exhibited a more profound invasion capacity in respiratory tissue compared to that in genital tissue at 24 h pi. However, at 24 h pi plaque latitude was found to be larger in genital tissue compared to respiratory tissue and this for all subtypes. These similar findings among the different subtypes take the edge off the belief of the existence of specific mucosa tropisms of different BoHV-1 subtypes.

  5. Effect of Antimicrobial Consumption and Production Type on Antibacterial Resistance in the Bovine Respiratory and Digestive Tract.

    Directory of Open Access Journals (Sweden)

    Boudewijn Catry

    Full Text Available The aim of this study was to investigate the relationship between antimicrobial use and the occurrence of antimicrobial resistance in the digestive and respiratory tract in three different production systems of food producing animals. A longitudinal study was set up in 25 Belgian bovine herds (10 dairy, 10 beef, and 5 veal herds for a 2 year monitoring of antimicrobial susceptibilities in E. coli and Pasteurellaceae retrieved from the rectum and the nasal cavity, respectively. During the first year of observation, the antimicrobial use was prospectively recorded on 15 of these farms (5 of each production type and transformed into the treatment incidences according to the (animal defined daily dose (TIADD and (actually used daily dose (TIUDD. Antimicrobial resistance rates of 4,174 E. coli (all herds and 474 Pasteurellaceae (beef and veal herds only isolates for 12 antimicrobial agents demonstrated large differences between intensively reared veal calves (abundant and inconstant and more extensively reared dairy and beef cattle (sparse and relatively stable. Using linear mixed effect models, a strong relation was found between antimicrobial treatment incidences and resistance profiles of 1,639 E. coli strains (p<0.0001 and 309 Pasteurellaceae (p≤0.012. These results indicate that a high antimicrobial selection pressure, here found to be represented by low dosages of oral prophylactic and therapeutic group medication, converts not only the commensal microbiota from the digestive tract but also the opportunistic pathogenic bacteria in the respiratory tract into reservoirs of multi-resistance.

  6. Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine.

    Science.gov (United States)

    Yang, Chin-Fen; Wang, C Kathy; Malkin, Elissa; Schickli, Jeanne H; Shambaugh, Cindy; Zuo, Fengrong; Galinski, Mark S; Dubovsky, Filip; Tang, Roderick S

    2013-06-10

    MEDI-534 is the first live vectored RSV vaccine candidate to be evaluated in seronegative children. It consists of the bovine parainfluenza virus type 3 (PIV3) genome with substituted human PIV3 F and HN glycoproteins engineered to express RSV F protein. A Phase 1 study of 49 healthy RSV and PIV3 seronegative children 6 to <24 months of age demonstrated an acceptable safety profile at the following doses: 10(4), 10(5) and 10(6)TCID50. After 3 doses of MEDI-534 at 10(6)TCID50, administered at 0, 2 and 4 month intervals, 100% of subjects seroresponded to PIV3, whereas only 50% seroresponded to RSV. To investigate the discordance in seroresponse rates, the RSV F transgene and its flanking non-coding nucleotides were sequenced from shed virus recovered from the nasal washes of 24 MEDI-534-vaccinated children. Eleven out of 24 samples contained no nucleotide changes in the analyzed region. The other 13 samples contained mixtures of variant subpopulations. Fifty-five percent exhibited changes in the transcription termination poly A gene sequences of the upstream bPIV3N gene while 21% had variant subpopulations in the RSV F open reading frame that resulted in pre-mature stop codons. Both types of changes are expected to reduce RSV F expression. Evaluation of the administered vaccine by dual immunofluorescence staining showed ~2.5% variants with low or no RSV F expression while single nucleotide primer extension detected ~1% variation at nucleotide 2045 that resulted in a pre-mature translational termination at codon 85. An association between shedding of variants and lower RSV F serological response was observed but it was not possible to establish a definitive clinical significance due to the small number of subjects in this study.

  7. Pharmacokinetic and pharmacodynamic testing of marbofloxacin administered as a single injection for the treatment of bovine respiratory disease.

    Science.gov (United States)

    Vallé, M; Schneider, M; Galland, D; Giboin, H; Woehrlé, F

    2012-12-01

    New approaches in Pharmacokinetic/Pharmacodynamic (PK/PD) integration suggested that marbofloxacin, a fluoroquinolone already licensed for the treatment of bovine respiratory disease at a daily dosage of 2 mg/kg for 3-5 days, would be equally clinically effective at 10 mg/kg once (Forcyl(®)), whilst also reducing the risk of resistance. This marbofloxacin dosage regimen was studied using mutant prevention concentration (MPC), PK simulation, PK/PD integration and an in vitro dynamic system. This system simulated the concentration-time profile of marbofloxacin in bovine plasma established in vivo after a single 10 mg/kg intramuscular dose and killing curves of field isolated Pasteurellaceae strains of high (minimum inhibitory concentration (MIC) MIC ≤ 0.03 μg/mL), average (MIC of 0.12-0.25 μg/mL) and low (MIC of 1 μg/mL) susceptibility to marbofloxacin. The marbofloxacin MPC values were 2- to 4-fold the MIC values for all Mannheimia haemolytica, Pasteurella multocida tested. Marbofloxacin demonstrated a concentration-dependent killing profile with bactericidal activity observed within 1 h for most strains. No resistance development (MIC ≥ 4 μg/mL) was detected in the dynamic tests. Target values for risk of resistance PK/PD surrogates (area under the curve (AUC) AUC(24 h) /MPC and T(>MPC) /T(MSW) ratio) were achieved for all clinically susceptible pathogens. The new proposed dosing regimen was validated in vitro and by PK/PD integration confirming the single-injection short-acting antibiotic concept.

  8. A stochastic model to determine the economic value of changing diagnostic test characteristics for identification of cattle for treatment of bovine respiratory disease.

    Science.gov (United States)

    Theurer, M E; White, B J; Larson, R L; Schroeder, T C

    2015-03-01

    Bovine respiratory disease is an economically important syndrome in the beef industry, and diagnostic accuracy is important for optimal disease management. The objective of this study was to determine whether improving diagnostic sensitivity or specificity was of greater economic value at varied levels of respiratory disease prevalence by using Monte Carlo simulation. Existing literature was used to populate model distributions of published sensitivity, specificity, and performance (ADG, carcass weight, yield grade, quality grade, and mortality risk) differences among calves based on clinical respiratory disease status. Data from multiple cattle feeding operations were used to generate true ranges of respiratory disease prevalence and associated mortality. Input variables were combined into a single model that calculated estimated net returns for animals by diagnostic category (true positive, false positive, false negative, and true negative) based on the prevalence, sensitivity, and specificity for each iteration. Net returns for each diagnostic category were multiplied by the proportion of animals in each diagnostic category to determine group profitability. Apparent prevalence was categorized into low (diagnostic specificity, perhaps through a confirmatory test interpreted in series or pen-level diagnostics, can increase diagnostic value more than improving sensitivity. Mortality risk was the primary driver for net returns. The results from this study are important for determining future research priorities to analyze diagnostic techniques for bovine respiratory disease and provide a novel way for modeling diagnostic tests.

  9. Evidence-based effectiveness of vaccination against Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in feedlot cattle for mitigating the incidence and effect of bovine respiratory disease complex.

    Science.gov (United States)

    Larson, R L; Step, D L

    2012-03-01

    Bovine respiratory disease complex is the leading cause of morbidity and mortality in feedlot cattle. A number of vaccines against bacterial respiratory pathogens are commercially available and researchers have studied their impact on morbidity, mortality, and other disease outcome measures in feedlot cattle. A systematic review will provide veterinarians with a rigorous and transparent evaluation of the published literature to estimate the extent of vaccine effect. Unfortunately, the published body of evidence does not provide a consistent estimate of the direction and magnitude of effectiveness in feedlot cattle vaccination against Mannheimia haemolytica, Pasteurella multocida, or Histophilus somni.

  10. Effects of injectable trace minerals on humoral and cell-mediated immune responses to Bovine viral diarrhea virus, Bovine herpes virus 1 and Bovine respiratory syncytial virus following administration of a modified-live virus vaccine in dairy calves.

    Science.gov (United States)

    Palomares, R A; Hurley, D J; Bittar, J H J; Saliki, J T; Woolums, A R; Moliere, F; Havenga, L J; Norton, N A; Clifton, S J; Sigmund, A B; Barber, C E; Berger, M L; Clark, M J; Fratto, M A

    2016-10-01

    Our objective was to evaluate the effect of an injectable trace mineral (ITM) supplement containing zinc, manganese, selenium, and copper on the humoral and cell mediated immune (CMI) responses to vaccine antigens in dairy calves receiving a modified-live viral (MLV) vaccine containing BVDV, BHV1, PI3V and BRSV. A total of 30 dairy calves (3.5 months of age) were administered a priming dose of the MLV vaccine containing BHV1, BVDV1 & 2, BRSV, PI3V, and an attenuated-live Mannheimia-Pasteurella bacterin subcutaneously (SQ). Calves were randomly assigned to 1 of 2 groups: (1) administration of ITM SQ (ITM, n=15) or (2) injection of sterile saline SQ (Control; n=15). Three weeks later, calves received a booster of the same vaccine combination SQ, and a second administration of ITM, or sterile saline, according to the treatment group. Blood samples were collected on days 0, 7, 14, 21, 28, 42, 56, and 90 post-vaccination for determination of antibody titer, viral recall antigen-induced IFN-γ production, and viral antigen-induced proliferation by peripheral blood mononuclear cells (PBMC). Administration of ITM concurrently with MLV vaccination resulted in higher antibody titers to BVDV1 on day 28 after priming vaccination compared to the control group (P=0.03). Calves treated with ITM showed an earlier enhancement in PBMC proliferation to BVDV1 following vaccination compared to the control group. Proliferation of PBMC after BVDV stimulation tended to be higher on day 14 after priming vaccination in calves treated with ITM than in the control group (P=0.08). Calves that received ITM showed higher PBMC proliferation to BRSV stimulation on day 7 after priming vaccination compared to the control group (P=0.01). Moreover, calves in the ITM group also had an enhanced production IFN-γ by PBMC after stimulation with BRSV on day 21 after priming vaccination compared to day 0 (P<0.01). In conclusion, administration of ITM concurrently with MLV vaccination in dairy calves resulted in increased antibody titer to BVDV1, and greater PBMC proliferation to BVDV1 and BRSV recall stimulation compared to the control group, suggesting that ITM might represent a promising tool to enhance the humoral and CMI responses to MLV vaccines in cattle.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    understanding of the virus. In this study, a BRSV fluorogenic reverse transcription PCR (fRT-PCR) assay, based on TaqMan principle, was developed and evaluated on a large number of clinical samples, representing various cases of natural and experimental BRSV infections. By using a single-step closed-tube format...

  12. 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

  13. Cattle with increased severity of bovine respiratory disease complex exhibit decreased capacity to protect against histone cytotoxicity.

    Science.gov (United States)

    Matera, J A; Wilson, B K; Hernandez Gifford, J A; Step, D L; Krehbiel, C R; Gifford, C A

    2015-04-01

    Bovine respiratory disease complex (BRDC) is the leading cause of morbidity and mortality in feedlot cattle. Significant inflammation and lesions are often observed in lungs of infected cattle. During acute inflammatory responses, histones contribute to mortality in rodents and humans and serum proteins can protect against histone-induced cytotoxicity. We hypothesized that cattle experiencing chronic or fatal cases of BRDC have reduced ability to protect against cytotoxic effects of histones. Serum samples were collected from 66 bull calves at the time of normal feedlot processing procedures. Animals were retrospectively assigned to groups consisting of calves never treated for BRDC (control [CONT]; n = 10), calves treated with antimicrobials once for BRDC (1T; n = 16), calves treated twice for BRDC (2T; n = 13), calves treated 3 times for BRDC (3T; n = 14), or calves treated 4 times for BRDC (4T; n = 13). Samples were also collected each time animals received antimicrobial treatment; animals within a group were further sorted by calves that recovered and calves that died to test histone cytotoxicity. Bovine kidney cells were cultured in duplicate in 96-well plates and exposed to 0 or 50 μg/mL of total histones for 18 h with 1% serum from each animal. Cell viability was assessed by the addition of resazurin for 6 h followed by fluorescent quantification. Fluorescent values from serum alone were subtracted from values obtained for histone treatment for each animal. Serum from CONT, 1T, and 2T at initial processing all exhibited a similar (P > 0.10) response to histone treatment with fluorescent values of -312 ± 557, -1,059 ± 441, and -975 ± 489, respectively. However, 3T and 4T demonstrated an impaired capacity (P < 0.05) to protect against histones (-2,778 ± 471 and -3,026 ± 489) at initial processing when compared to the other groups. When sorted by mortality within group, calves that were treated twice and recovered (-847 ± 331) demonstrated a greater (P

  14. Treatment of naturally occurring bovine respiratory disease in juvenile calves with a single administration of a florfenicol plus flunixin meglumine formulation.

    Science.gov (United States)

    Thiry, J; González-Martín, J V; Elvira, L; Pagot, E; Voisin, F; Lequeux, G; Weingarten, A; de Haas, V

    2014-04-26

    The efficacy and safety of a florfenicol plus flunixin meglumine formulation in the treatment of respiratory disease was evaluated in calves less than six weeks of age, compared with a positive control group treated with a well-established florfenicol formulation. A total of 210 calves, selected from nine sites in Belgium, France and Spain, showing severe signs of respiratory disease, were randomly assigned to treatment with either florfenicol plus flunixin meglumine (Resflor; MSD Animal Health) or florfenicol (Nuflor; MSD Animal Health), both administered subcutaneously once. Animals were clinically observed daily for 10 days following treatment initiation. The predominant respiratory pathogens were Pasteurella multocida, Mycoplasma bovis, Mannheimia haemolytica and Histophilus somni. All isolates were subject to in vitro sensitivity testing and found susceptible to florfenicol. In both groups, rectal temperature dropped and clinical index (depression and respiratory signs) significantly improved after treatment. Specifically, for the change in rectal temperature from pretreatment to six hours post-treatment, the florfenicol-flunixin formulation was found significantly superior to florfenicol. Moreover, the florfenicol-flunixin formulation alleviated the clinical signs of disease more rapidly, and was demonstrated to be non-inferior to florfenicol on days 4 and 10. The use of the product combining florfenicol and flunixin in calves is safe and efficacious in the treatment of outbreaks of bovine respiratory disease.

  15. 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

  16. Relationship between respiratory syncytial virus bronchiolitis and bronchial asthma%呼吸道合胞病毒毛细支气管炎与支气管哮喘的相关性研究

    Institute of Scientific and Technical Information of China (English)

    李宾; 吴福玲; 冯学斌; 韩兆东; 李营营; 石涛

    2012-01-01

    Objective To explore the relationship between bronchiolitis caused by respiratory syncytial virus (RSV) and bronchial asthma. Methods The levels of interferon-γ (IFN-7) , interleukin-4 (IL-4) , interleukin-10 (IL-10), transforming growth factor-13 (TGF-|3) and interleukin-17 (IL-17) in 31 infants with RSV bronchiolitis, 25 infants with asthma, 27 infants with non-RSV pneumonia and 24 healthy infants were detected by ELISA. Results IL-10 and TGF-P levels in infants with RSV bronchiolitis and infants with asthma were significantly lower than those in the non-RSV pneumonia group and the normal control group (P 0.05) , and also no significant differences were observed between the common pneumonia group and the normal control group ( P > 0.05) . Conclusions The same changes of the levels of IFN-γ, IL-4, IL-10, TGF-P and IL-17 in infants with RSV bronchiolitis and infants with asthma may be a common pathogenesis of RSV bronchiolitis and asthma.%目的 探讨呼吸道合胞病毒(RSV)毛细支气管炎(毛支)与支气管哮喘两者发病机制的相关性.方法采用ELISA法检测31例RSV毛支患儿、25例支气管哮喘患儿、27例非RSV肺炎患儿和24例健康儿童外周血IFN-γ、IL-4、IL-10、TGF-β、IL-17水平,并进行比较分析.结果 RSV毛支患儿和哮喘患儿的IL-10、TGF-β水平显著低于非RSV肺炎患儿和健康对照儿童,而IL-4、IL-17水平则显著高于非RSV肺炎患儿和健康对照儿童(P均< 0.05).RSV毛支患儿和哮喘患儿的IFN-γ/IL-4、IL-10/IL-17比例显著低于非RSV肺炎患儿和健康对照儿童(P均<0.05),哮喘患儿的TGF-β/IL-17显著低于非RSV肺炎患儿与健康对照儿童(P均<0.05).RSV毛支患儿与哮喘患儿之间、非RSV肺炎患儿与健康对照儿童之间IFN-γ、IL-4、IL-10、TGF-β、IL-17水平及其比值IFN-γ/IL-4、IL-10/IL-17、TGF-β/IL-17的差异均无统计学意义(P均>0.05).结论 RSV毛支患儿与哮喘患儿存在相同的外周血细胞因子IFN-γ、IL-4

  17. A Systematic Review of Bovine Respiratory Disease Diagnosis Focused on Diagnostic Confirmation, Early Detection, and Prediction of Unfavorable Outcomes in Feedlot Cattle.

    Science.gov (United States)

    Wolfger, Barbara; Timsit, Edouard; White, Brad J; Orsel, Karin

    2015-11-01

    A large proportion of newly arrived feedlot cattle are affected with bovine respiratory disease (BRD). Economic losses could be reduced by accurate, early detection. This review evaluates the available literature regarding BRD confirmatory diagnostic tests, early detection methods, and modalities to estimate post-therapeutic prognosis or predict unfavorable or fatal outcomes. Scientific evidence promotes the use of haptoglobin to confirm BRD status. Feeding behavior, infrared thermography, and reticulorumen boluses are promising methods. Retrospective analyses of routinely collected treatment and cohort data can be used to identify cattle at risk of unfavorable outcome. Other methods have been reviewed but require further study.

  18. Clinical characteristics and use of antibiotics in severe respiratory syncytial virus pneumonia%重症呼吸道合胞病毒肺炎临床特点及抗菌药物使用分析

    Institute of Scientific and Technical Information of China (English)

    林洁; 董琳; 李海燕; 万春杰; 陈小芳

    2011-01-01

    Objectives To investigate the clinical characteristics and use of antibiotics in severe respiratory syncytial virus (RSV) pneumonia in children. Methods Retrospective analysis of clinical and etiological data was performed in children with severe RSV pneumonia admitted to our hospital from January 2005 to December 2009.Results Among total of 4189 cases of RSV infection, 306 patients (7.3%) met the diagnostic criteria of severe pneumonia; 214 were male and 92 were female, aged from 8 days to 4 years old. The proportion of patients younger than 6 months was 81.0%. Overall, 161 (52.6%) had respiratory failure, 22 (7.2%) developed heart failure, 7 (2.3%) had toxic encephalopathy, 3 (1.0%) developed sepsis and multiple organ dysfunction, 1 had septic shock and alimentary tract hemorrhage. 126 (41.2%) were admitted to ICU, of which 36 (11.8%) were applied mechanical ventilation. Underlying diseases were observed in 217 (70.9%) patients, they are congenital heart disease, followed by premature birth and low birth weight, malnutrition, and nervous system disease. All cases were performed sputum pathogen detections and 51 were also got blood cultures. Combined pathogenic infection were found in 102 cases (33.3%). In sputum 129 strains of pathogens were identified, of which 114 strains were bacteria, the predominant one was Gram-negative bacteria (69.0%), followed by Gram-positive bacteria (19.4%); blood culture were positive in 3 cases. All patients were treated with antibiotics, the use of cephalosporins utilization was up to 88.9%. The use of one antibiotic accounted for 63.4%, while the combination of two antibiotics accounted for 35.0%. Using of antibiotics in 68 cases (22.2%) was less than one week, 168 (54.9%) were between one to two weeks. The outcome are 217 cases cured, 81 improved, and 1 died. Conclusions RSV was the most important pathogenic virus in severe pneumonia in children. Severe RSV pneumonia were mainly seen in infants

  19. Infecções do trato respiratório inferior pelo vírus sincicial respiratório em crianças hospitalizadas menores de um ano de idade Respiratory syncytial vírus - associated lower respiratory tract infections in hospitalized infants

    Directory of Open Access Journals (Sweden)

    Cláudio D'Elia

    2005-02-01

    Full Text Available Analisou-se características clínicas e evolutivas em crianças menores de um ano internadas com infecção do trato respiratório inferior por vírus sincicial respiratório (VSR. Feito estudo transversal com 89 lactentes hospitalizados durante as épocas de maior incidência do VSR, em 1997 e 1998, na cidade do Rio de Janeiro. Foram pesquisados antígenos virais, nas secreções de nasofaringe, com anticorpos monoclonais anti-VSR, antiinfluenza A e B e antiparainfluenza tipo 3, por ensaio de imunofluorescência indireta. Formaram-se três grupos: bronquiolite ou bronquite sibilante (n=44, pneumonia (n=26 e bronquiolite e pneumonia (n=19. Houve positividade para o VSR em 42 (47,1% pacientes. Em 1997 a média de dias de oxigenoterapia foi de 5,2 e em 1998, de 2,5 dias (p> 0,05. Não houve diferença de apresentação clínica entre os lactentes que apresentaram positividade para o VSR e aqueles cujo resultado foi negativo. A sensibilidade e especificidade da sibilância em relação ao isolamento de VSR foram 85% e 65%, respectivamente. O VSR foi o principal causador de infeções do trato respiratório inferior em lactentes que necessitaram de hospitalização.For analysis of clinical features and outcome of hospitalized infants with respiratory syncytial virus lower respiratory tract infection, was carried out. Cross-sectional study with 89 infants, hospitalized in two public hospitals during the 1997 and 1998 RSV seasons, in Rio de Janeiro city. Nasopharyngeal secretions were obtained and specimens processed for viral antigens detection by indirect immunofluorescence assay with the use of anti RSV, antiinfluenza A and B and anti parainfluenza type 3 monoclonal antibodies. Patients were allocated into three diagnostic groups: bronchiolitis or wheeze bronchitis (n = 44; Pneumonia (n = 26 and bronchiolitis or wheeze bronchitis and pneumonia (n = 19. Positivity for RSV was found in 42 (47.1% patients. More days of hospitalization were seen in

  20. 抗呼吸道合胞病毒Fab噬菌体抗体库的构建及初步筛选%Construction and preliminary panning of Fab phage display antibody library against respiratory syncytial virus

    Institute of Scientific and Technical Information of China (English)

    汪治华; 张国成; 李安茂; 周南; 陈一; 李小青; 苏字飞; 邓阳彬; 王治静

    2008-01-01

    Objective To construct a human phage display antibody library,which will help to develop new drugs and vaccines against respiratory syncytial virus (RSV) and solve many of the issues that have limited the progression and application of murine monoclonal antibodies (McAbs) in the clinic.This can provide a platform for human antibody preparation and diagnosis,prophylaxis and therapy of RSV infection in children.Methods Peripheral blood lymphocytes were isolated from 52 children with RSV infection,cDNA was synthesized from the total RNA of lymphocytes.The light and heavy chain Fd (VH-CH1)fragments of immunoglobulin gene were amplified by RT-PCR.The amplified products were cloned into phagemid vector pComb3x and the clone samples were electrotransformed into competent E.coli XL1-Blue.The transformed cells were then infected with M13K07 helper phage to yield recombinant phage antibody of Fabs.The plasmids extracted from amplified E.coil were digested with restriction endonucleases Sac 1,Xba I,Spe I and Xho I to monitor the insertion of the light or heavy chain Fd genes.RSV virions were utilized as antigens to screen Fab antibodies.Results By recombination of light and heavy chain genes,an immune Fab phage display antibody library against RSV containing 2.08×107 different clones was constructed,in which 70% clones had light chains and heavy chain Fd genes.The capacity of Fab phage antibody gene library was 1.46×107 and the titre of the original Fab antibody library was about 1.06 x 1012 pfu/mL The antibody library gained an enrichment in different degrees after the preliminary panning.Condusions Utilizing the technology of phage display,an immune Fab phage display antibody library against RSV was successfully constructed in this study,which laid a valuable experimental foundation for further study and created favorable conditions for preparing human McAbs. This may also contribute to the improvement in the diagnosis,therapy and prophylaxis of RSV infection in children

  1. Bovine viral diarrhea (BVD) can open the door to other problems, including reproductive, respiratory, and enteric disease

    Science.gov (United States)

    This is a review, written for a lay publication whose core audience in dairy producers. A brief history of bovine viral diarrhea (BVD) research is given as well as a review of recent research discoveries. National efforts to reduce antibiotic use have led to a greater emphasis on disease prevention ...

  2. 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

  3. Some viral and bacterial respiratory tract infections of dairy cattle during the summer season

    Directory of Open Access Journals (Sweden)

    Kale M.

    2013-01-01

    Full Text Available In this research, dairy cattle with respiratory system problems that were brought to a private slaughterhouse in Burdur province were investigated for viral and bacterial infections present in the summer season. The blood samples were collected from 56 animals. The samples were tested for antibodies against bovine herpesvirus 1 (BoHV-1, bovine viral diarrhea virus (BVDV, bovine respiratory syncytial virus (BRSV, bovine parainfluenza virus 3 (BPIV-3 and bovine adenovirus 3 (BAV-3 by ELISA. Bacteriological cultivation was carried out from lung samples taken after cutting the same animals. The seropositivity rates which were determined for 5 viruses in cattle (BoHV- 1, BVDV, BRSV, BPIV-3 and BAV-3 were 7.14%, 50%, 94.64%, 94.64% and 82.14% respectively. The presence of antibodies against the viruses was as follows; 5.36% of cattle had antibodies against only one virus, 14.29% against two, 30.36% against three, 44.64% against four and 5.36% against five viruses. A total of 36 bacterial agents were isolated from 30 out of 56 lung samples. From the lung samples, only one bacterium was isolated from 39.3% (22/56 samples, and more than one bacterium from 14.3% (8/56. Escherichia coli, Staphylococcus aureus and Streptococcus spp. were detected as the most often isolated agents. Compared to bacteria, the rates of viral infections associated with Escherichia coli (BRSV+BPIV-3+BAV- 3+Escherichia coli; 8.92% and BRSV+BPIV-3+Escherichia coli; 5.35% were higher. As a consequence, it was thought that primary agents which were the viruses and bacteria may have attended as secondary factors in respiratory tract infections of dairy cattle.

  4. Toll-like receptor-associated mechanism in respiratory syncytial virus vaccine-enhanced disease%Toll 样受体通路激活改善呼吸道合胞病毒疫苗诱导免疫应答的研究进展

    Institute of Scientific and Technical Information of China (English)

    贾然; 徐锦

    2015-01-01

    Respiratory syncytial virus (RSV) is the most important pathogen responsible for children ’s severe lower respiratory tract infection worldwide . However , no vaccine has been licensed to prevent RSV infection as the inactivated RSV vaccine could enhance disease severity . The exact mechanism of RSV vaccine‐enhanced disease (RVED) remains unclear .Since Toll‐like receptors (TLRs) and their signal pathways play crucial roles in both innate and adaptive immunity ,TLR‐associated RVED mechanism has been proposed and is attracting more and more attentions of researchers .In this review ,we summarized the main progress on the roles of TLRs in anti‐RSV immunity and their signal pathways in affecting the immune status of mice with RVED ,which may enlighten the vaccine design and development .%呼吸道合胞病毒(RSV)是导致婴幼儿严重下呼吸道感染的最重要病原体,但该病毒的灭活疫苗可引起RSV疫苗增强性疾病(RVED)。RVED的机制目前仍不清楚。Toll样受体(TLR)及其信号转导对 RSV的识别和宿主免疫的激发均有重要作用,其在RVED机制中的作用也日益受到关注。本文主要介绍TLR在抗RSV天然免疫和获得性免疫中的角色及其信号通路激活状态改变对RVED免疫格局的影响,提示RVED机制可能与TLR信号通路激活不足有关,从而为RSV疫苗研制提供新的策略和方法。

  5. A comparison of clinical features between rhinovirus and respiratory syncytial virus infection in lower respiratory ;tract in children%下呼吸道鼻病毒与呼吸道合胞病毒感染临床特征比较

    Institute of Scientific and Technical Information of China (English)

    孙秋凤; 陈正荣; 黄莉; 朱灿红; 王宇清; 王美娟; 季伟; 邵雪君; 严永东

    2014-01-01

    Objectives To compare the clinical features between rhinovirus and respiratory syncytial virus infection in lower respiratory tract in children. Methods From December 2012 to May 2013, direct immunofluorescence assay was per-formed to test RSV in 1 037 nasal aspirate specimens with LRTIs. RT-PCR method was used to test HRV RNA. The medical re-cords of patients with a positive test of HRV or RSV were reviewed and compared. Results The isolating rate for HRV and RSV was 8.78%(91/1 037) and 17.16%(178/1 037) respectively. The frequency of co-infection of HRV with other virus was 18.68%, higher than that of RSV (7.30%,χ2=7.867, P=0.005). The age distribution had significant difference between children infected with HRV and RSV (Z=5.40, P<0.001). 78.38% patients with HRV infection were younger than 3 years old, and 83.03%patients with RSV infection were younger than 1 year old. Dyspnea, hyoxemia and wheezing were more common in pa-tients with RSV infection. Admission occurred much later in the course of the HRV infection (P<0.01). Leukocytosis, eosinophi-lia, and an elevated total serum IgE were more common in patients with HRV infection (P<0.05). Conclusions HRV is one of the important causes of LRTIs in Suzhou. The susceptible population, clinical presentation and laboratory results of HRV infec-tions are different from that of RSV infections.%目的:比较下呼吸道鼻病毒(HRV)与呼吸道合胞病毒(RSV)感染患儿的临床特点。方法采集2012年12月至2013年5月住院的1037例下呼吸道感染患儿的鼻咽分泌物,应用直接免疫荧光法检测RSV抗原,RT-PCR法检测HRV RNA,并分析比较HRV及RSV感染患儿的临床特点。结果 HRV及RSV检出阳性率分别为8.78%(91/1037)和17.16%(178/1037),其中HRV与其他呼吸道病毒的混合感染率为18.68%,RSV为7.30%,两者差异有统计学意义(χ2=7.87,P=0.005)。HRV与RSV感染患儿的年龄分布差异有统计学意义(Z=5.40,P<0.001

  6. RSV与HRV在ALRTI住院儿童中的流行状况和临床特征比较%Comparative analysis of epidemiology and clinical characteristic on respiratory syncytial virus and human rhinovirus in hospitalized children with acute lower respiratory infections

    Institute of Scientific and Technical Information of China (English)

    王涛; 张兵; 肖霓光; 谢志萍; 钟礼立; 黄寒; 曾赛珍; 段招军

    2012-01-01

    目的:了解RSV和HRV在ALRTI住院儿童中流行病学和临床特征的异同.方法:收集2007年9月~2008年8月ALRTI住院患儿NPA样本,进行病毒核酸检测,统计分析RSV和HRV检出病例的流行状况、临床特点.结果:1165名患儿裣出RSV 315例(27.0%),HRV 202例(17.3%);性别之间检出率无统计学差异;RSV检出患儿平均年龄13.1±14.3月,1岁以下检出率最高,且明显高于同年龄段HRV检出率;HRV检出患儿平均年龄15.8±17.8月,1岁检出率最高,并高于同年龄段RSV检出率;RSV检出以11月份到次年2月份为高峰;HRV检出以4月份、9~12月份为高峰;与RSV比较,HRV检出病例临床特点除末梢血白细胞计数升高较多见外,其它均无差异;与单一RSV检出病例比较,RSV混合其它病毒检出病例并发症较多,且末梢血白细胞计数升高较多见;单一HRV检出病例未见发绀,其余临床特点与混合其它病毒检出病例无差异.结论:RSV和HRV是长沙地区ALRTI住院儿童的重要病原体,两者在年龄、季节分布上有不同,临床特点无明显差别.%To compare with the difference of epidemiology and clinical features between respiratory syncytial virus(RSV) and human rhinovirus(HRV) infection in hospit- alized children with acute lower respiratory tract infection (ALRTI) in Changsha. Methods 1165 nasopharyngeal aspirates (NPA)specimens were collected in hospitalized children with ALRTI from 2007.9 to 2008.8 in Changsha. Clinical characteristics and epidemiology fea-tures of RSV infections were compared with HRV infections in children. Results RSV was detected in 315 patients (27.04%) of the 1165 children., HRV was detected in 202 patie-nts (17.3%).There is no significant difference in detection rate between male and female (X2=0.079,P=0.778). The average age of RSV infected children was 13.1±14.3 month and The detected rate was the highest in children with less than 1 year old, The detected rateof RSV infections is

  7. Comparison of tulathromycin and tilmicosin on the prevalence and severity of bovine respiratory disease in feedlot cattle in association with feedlot performance, carcass characteristics, and economic factors.

    Science.gov (United States)

    Tennant, T C; Ives, S E; Harper, L B; Renter, D G; Lawrence, T E

    2014-11-01

    The objectives of this study were to 1) quantify effects of metaphylactic treatment for bovine respiratory disease (BRD) on growth performance, carcass characteristics, and lung lesion prevalence and severity; 2) evaluate the association of lung lesion prevalence and severity with carcass characteristics; and 3) evaluate effects of therapeutic treatment on carcass characteristics and lung lesion prevalence and severity. The study was conducted at a commercial feedlot in the Texas Panhandle in which steers (n = 2,336) initially weighing 312.1 ± 9.6 kg were sourced from auction markets and allocated in a randomized complete block design to 1 of 3 treatments (no metaphylactic [no antimicrobial drug {ND}] treatment, tilmicosin at 10 mg/kg BW [TIL], and tulathromycin at 2.5 mg/kg BW [TUL]). Lungs of all steers were evaluated during harvest to assess presence and severity of pneumonic lesions in the anteroventral lobes and the presence and severity of pleural adherences. Compared to the ND treatment, steers treated via metaphylactic therapy had greater (P cattle, cumulatively resulting in greater financial returns. Lung lesions were present in 64.3% of lungs and were distributed similarly between metaphylactic treatments (63.9%) and ND (65.1%) cattle. Steers with advanced lung lesions present at harvest were associated with reduced (P cattle improved financial returns primarily driven by reductions in cost of death loss and railers.

  8. Mixed infection of peste des petits ruminants virus (PPRV) and other respiratory viruses in dromedary camels in Sudan, an abattoir study.

    Science.gov (United States)

    Saeed, Intisar Kamil; Ali, Yahia Hassan; AbdulRahman, Magdi Badawi; Mohammed, Zakia Abas; Osman, Halima Mohammed; Taha, Khalid Mohammed; Musa, Mohammed Zain; Khalafalla, AbdelMelik Ibrahim

    2015-06-01

    This study was intended to determine the role played by peste des petits ruminants (PPR) in causing respiratory infections in camels and its association with other respiratory viruses. A total of 474 lung specimens showing pneumonia were collected from clinically healthy camels in slaughterhouses at five different areas in Sudan. Using immunocapture ELISA (IcELISA), 214 specimens (45.1 %) were found to be positive for PPR antigen. The highest prevalence was found in central Sudan (59.9 %) then northern Sudan (56.6 %) and eastern Sudan (26.6 %). Parainfluenza virus 3 (PIV 3), respiratory syncytial virus (RSV), bovine herpes virus-1 (BHV-1), bovine viral diarrhea (BVD), and adenovirus were detected in 4.4, 2.9, 2.0, 9.0, and 1.3 % of the specimens, respectively. PPR antigen was found in about 50 % of specimens that showed positive result for other viral antigens. Twenty-five of 28 BVD, 15 of 16 PIV3, 8 of 12 RSV, 4 of 4 adenovirus, and 4 of 5 BHV-1 were found in association with other respiratory antigens. Results revealed the existence of PPRV infection in dromedary camels in Sudan and present evidence for mixed virus infection, suggesting that respiratory infections in camels might be exacerbated by PPRV.

  9. Concentrações de interleucina-2 na secreção nasofaríngea de crianças com bronquiolite viral aguda pelo vírus respiratório sincicial Concentrations of interleukin-2 in the nasopharyngeal secretion of children with acute respiratory syncytial virus bronchiolitis

    Directory of Open Access Journals (Sweden)

    Katia M. Giugno

    2004-08-01

    Full Text Available OBJETIVO: Avaliar as concentrações de interleucina-2 (IL-2 na secreção nasofaríngea de crianças (0-24 meses acometidas de bronquiolite viral aguda pelo vírus respiratório sincicial nas primeiras 12 horas de hospitalização e correlacionar os níveis encontrados com a gravidade da doença. MÉTODOS: Estudo prospectivo com amostragem seqüencial realizado no período de junho a agosto de 1999. Foram incluídos 62 pacientes previamente hígidos, internados com diagnóstico de bronquiolite viral aguda caracterizado por pródromos recentes de coriza e/ou obstrução nasal que evoluíram com pelo menos dois dos seguintes sinais: disfunção respiratória, taquipnéia, sibilos ou crepitações. Todos os pacientes tiveram a presença de vírus respiratório sincicial detectada no aspirado nasofaríngeo. As amostras de secreção nasofaríngea foram obtidas nas primeiras 12 horas de hospitalização. As dosagens de IL-2 foram realizadas por ensaio imunoenzimático. A gravidade da doença foi avaliada por: medida da saturação de oxigênio da hemoglobina por oximetria de pulso, sistema de escore clínico modificado, tempo de uso de oxigênio, tempo de hospitalização e necessidade de ventilação mecânica, sendo estas variáveis comparadas em relação às medianas de IL-2 através dos testes de Spearman e Kruskal-Wallis e, para a análise categorizada da interleucina, através do teste de qui-quadrado. RESULTADOS: A mediana de idade dos pacientes foi 2,2 (1,3-4 meses. O sexo masculino foi observado em 54% dos casos. Saturação de oxigênio da hemoglobina por oximetria de pulso na hospitalização foi OBJECTIVE: To assess interleukin-2 concentrations in nasopharyngeal secretion of children (0-24 months with acute respiratory syncytial virus bronchiolitis, within the first 12 hours of hospital admission, and compare the levels of IL-2 with the severity of the illness. METHODS: Prospective study performed between June and August 1999. The study

  10. The Prevalence and Control of Bovine Respiratory Disease Complex%牛呼吸疾病综合征及其防治

    Institute of Scientific and Technical Information of China (English)

    郭爱珍

    2011-01-01

    Bovine respiratory disease complex(BRD) is a most costly disease in beef industry.It is a multifactor disease caused by pathogens such as Mycoplasma,viruses and bacteria,transport stress,etc.The developed countries such as America began to study this disease in early 1980's,and the research and control for BRD have reached a high level of platform.However,BRD is still thought to be the most important disease for cattle in the next 10 to 20 years.China just began to realize the impact of BRD to the cattle industry in recent years and study the prevalence and control.To learn the experience and knowledge from the developed countries would help China to improve the control of BRD in cattle.%牛呼吸疾病综合征是严重危害国内外肉牛养殖业的一种重要传染病,该病的致病因素复杂,包括支原体、病毒和细菌等特异性病原以及运输应激等多种因素。美国等发达国家对该病的攻关研究开始于上世纪80年代初,其研究和临床防控均已达到较高水平,但仍认为该病将是未来10~20年养牛业所面临的主要疾病。我国对该病的认识和研究尚处于起步阶段,借鉴世界上发达国家的先进经验将有助于提升我国对该病的防控水平。

  11. Bayesian evaluation of clinical diagnostic test characteristics of visual observations and remote monitoring to diagnose bovine respiratory disease in beef calves.

    Science.gov (United States)

    White, Brad J; Goehl, Dan R; Amrine, David E; Booker, Calvin; Wildman, Brian; Perrett, Tye

    2016-04-01

    Accurate diagnosis of bovine respiratory disease (BRD) in beef cattle is a critical facet of therapeutic programs through promotion of prompt treatment of diseased calves in concert with judicious use of antimicrobials. Despite the known inaccuracies, visual observation (VO) of clinical signs is the conventional diagnostic modality for BRD diagnosis. Objective methods of remotely monitoring cattle wellness could improve diagnostic accuracy; however, little information exists describing the accuracy of this method compared to traditional techniques. The objective of this research is to employ Bayesian methodology to elicit diagnostic characteristics of conventional VO compared to remote early disease identification (REDI) to diagnose BRD. Data from previous literature on the accuracy of VO were combined with trial data consisting of direct comparison between VO and REDI for BRD in two populations. No true gold standard diagnostic test exists for BRD; therefore, estimates of diagnostic characteristics of each test were generated using Bayesian latent class analysis. Results indicate a 90.0% probability that the sensitivity of REDI (median 81.3%; 95% probability interval [PI]: 55.5, 95.8) was higher than VO sensitivity (64.5%; PI: 57.9, 70.8). The specificity of REDI (median 92.9%; PI: 88.2, 96.9) was also higher compared to VO (median 69.1%; PI: 66.3, 71.8). The differences in sensitivity and specificity resulted in REDI exhibiting higher positive and negative predictive values in both high (41.3%) and low (2.6%) prevalence situations. This research illustrates the potential of remote cattle monitoring to augment conventional methods of BRD diagnosis resulting in more accurate identification of diseased cattle.

  12. Relationship between rectal temperature at first treatment for bovine respiratory disease complex in feedlot calves and the probability of not finishing the production cycle.

    Science.gov (United States)

    Theurer, Miles E; White, Brad J; Larson, Robert L; Holstein, Krista K; Amrine, David E

    2014-12-01

    OBJECTIVE-To determine the relationship between rectal temperature at first treatment for bovine respiratory disease complex (BRDC) in feedlot calves and the probability of not finishing the production cycle. DESIGN-Retrospective data analysis. ANIMALS-344,982 calves identified as having BRDC from 19 US feedlots from 2000 to 2009. PROCEDURES-For each calf, data for rectal temperature at initial treatment for BRDC and various performance and outcome variables were analyzed. A binary variable was created to identify calves that did not finish (DNF) the production cycle (died or culled prior to cohort slaughter). A mixed general linear model and receiver operating characteristic curve were created to evaluate associations of rectal temperature, number of days in the feedlot at time of BRDC diagnosis, body weight, quarter of year at feedlot arrival, sex, and all 2-way interactions with rectal temperature with the probability that calves DNF. RESULTS-27,495 of 344,982 (7.97%) calves DNF. Mean rectal temperature at first treatment for BRDC was 40.0°C (104°F). As rectal temperature increased, the probability that a calf DNF increased; however, that relationship was not linear and was influenced by quarter of year at feedlot arrival, sex, and number of days in the feedlot at time of BRDC diagnosis. Area under the receiver operating characteristic curve for correct identification of a calf that DNF was 0.646. CONCLUSIONS AND CLINICAL RELEVANCE-Rectal temperature of feedlot calves at first treatment for BRDC had limited value as a prognostic indicator of whether those calves would finish the production cycle.

  13. Randomized, non-inferiority trial comparing a nitric oxide releasing solution with a macrolide antibiotic for control of bovine respiratory disease in beef feedlot calves at high-risk of developing respiratory tract disease.

    Science.gov (United States)

    Crepieux, T; Miller, C; Regev-Shoshani, G; Schaefer, A; Dorin, C; Alexander, T; Timsit, E

    2016-04-01

    Nitric oxide, a molecule produced in most mammalian cells, has bactericidal and virucidal properties. Nasal instillation of a nitric oxide releasing solution (NORS) on arrival at the feedlot was recently reported as non-inferior to a parenteral injection of a macrolide antibiotic, tilmicosin, for control of bovine respiratory disease (BRD) in cattle at low-to-moderate risk of developing BRD. The objective of this study was to evaluate whether NORS was non-inferior to tilmicosin for control of BRD in cattle at high-risk of developing BRD (the target population for many BRD control programs). High-risk Angus-cross heifers (n=840) were randomly allocated to 2 treatment groups on arrival at a feedlot and received either NORS or tilmicosin for BRD control. Non-inferiority was assessed by calculating the difference in prevalence of heifers diagnosed with BRD during the first 40 d after arrival between NORS and tilmicosin treatment groups. The non-inferiority margin (δ) was set at 8.5%. Thirty-six and 19% of heifers were diagnosed with BRD in the NORS and tilmicosin groups, respectively. Because the lower bound of the 2-sided 95% confidence interval (CI) of the difference in BRD prevalence between the 2 treatment groups (17%; 95% CI=11-23%) was higher than δ, an inferiority of NORS was concluded. Although on-arrival nasal administration of NORS can be viewed as a more rational control strategy than parental injection of antibiotics, further research is needed to improve NORS efficacy before it can be recommended to prevent BRD in high-risk cattle.

  14. Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk.

    Directory of Open Access Journals (Sweden)

    Gerco den Hartog

    Full Text Available BACKGROUND: Respiratory syncytial virus (RSV infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins. OBJECTIVE: To investigate whether IgG purified from bovine milk (bIgG can modulate immune responses against human RSV. METHODS: ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated. RESULTS: bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV. CONCLUSIONS: The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.

  15. Evaluating the cost implications of a radio frequency identification feeding system for early detection of bovine respiratory disease in feedlot cattle.

    Science.gov (United States)

    Wolfger, Barbara; Manns, Braden J; Barkema, Herman W; Schwartzkopf-Genswein, Karen S; Dorin, Craig; Orsel, Karin

    2015-03-01

    New technologies to identify diseased feedlot cattle in early stages of illness have been developed to reduce costs and welfare impacts associated with bovine respiratory disease (BRD). However, the economic value of early BRD detection has never been assessed. The objective was to simulate cost differences between two BRD detection methods during the first 61 d on feed (DOF) applied in moderate- to large-sized feedlots using an automated recording system (ARS) for feeding behavior and the current industry standard, pen-checking (visual appraisal confirmed by rectal temperature). Economic impact was assessed with a cost analysis in a simple decision model. Scenarios for Canadian and US feedlots with high- and low-risk cattle were modeled, and uncertainty was estimated using extensive sensitivity analyses. Input costs and probabilities were mainly extracted from publicly accessible market observations and a large-scale US feedlot study. In the baseline scenario, we modeled high-risk cattle with a treatment rate of 20% within the first 61 DOF in a feedlot of >8000 cattle in Canada. Early BRD detection was estimated to result in a relative risk of 0.60 in retreatment and 0.66 in mortality compared to pen-checking (based on previously published estimates). The additional cost of monitoring health with ARS in Canadian dollar (CAD) was 13.68 per steer. Scenario analysis for similar sized US feedlots and low-risk cattle with a treatment rate of 8% were included to account for variability in costs and probabilities in various cattle populations. Considering the cost of monitoring, all relevant treatment costs and sale price, ARS was more costly than visual appraisal during the first 61 DOF by CAD 9.61 and CAD 9.69 per steer in Canada and the US, respectively. This cost difference increased in low-risk cattle in Canada to CAD 12.45. Early BRD detection with ARS became less expensive if the costs for the system decreased to less than CAD 4.06/steer, or if the underlying true

  16. Estimating the comparative clinical and economic consequences of tulathromycin for treatment of present or anticipated outbreaks of bovine respiratory disease in feedlot cattle in the United States.

    Science.gov (United States)

    Nautrup, B Poulsen; Van Vlaenderen, I; Gasper, S M; Holland, R E

    2013-12-01

    The goal of this study was to determine the clinical and economic impact of using tulathromycin as first line treatment for bovine respiratory disease (BRD) compared with other commonly used antimicrobials. Two decision trees were developed simulating the consequences of treating cattle at high risk of developing BRD [control model (CM)] or cattle with first clinical BRD episode [treatment model (TM)]. As comparators florfenicol and tilmicosin were considered in both models whereas enrofloxacin was included in the TM because it was only labeled for treatment of BRD at the time of development of the calculators. A total of 5 (CM) and 10 (TM) comparative clinical studies that reported efficacy data for the selected drugs and indications were identified as suitable for model population. The following outcomes were considered: first treatment success, number of subsequent BRD treatments, chronics, and mortalities. Cost parameters were considered from the perspective of the producer and included treatment costs (first treatment and retreatments) and costs of chronics and deaths derived from published sources for 2010 (default). The models allowed the estimation of clinical and economic consequences according to each individual trial outcomes. Treatment with tulathromycin resulted in more first treatment successes and fewer removals (chronics and deaths) in all comparisons. The average total number of antimicrobial treatments required for the management of BRD was also least with tulathromycin as first treatment option. Because of better efficacy, total costs over the entire study periods were always lowest with tulathromycin. Depending on the study selected as the basis for the efficacy evaluation, cost savings with tulathromycin were calculated in the CM between US$21.00 and $47.86 (vs. florfenicol) and $11.37 and $72.64 (vs. tilmicosin); cost savings in the TM ranged between $28.47 and $143.87 (vs. florfenicol) and $7.75 and $84.91 (vs. tilmicosin) as well as between

  17. Prediction of respiratory disease and diarrhea in veal calves based on immunoglobulin levels and the serostatus for respiratory pathogens measured at arrival.

    Science.gov (United States)

    Pardon, Bart; Alliët, Jeroen; Boone, Randy; Roelandt, Sophie; Valgaeren, Bonnie; Deprez, Piet

    2015-06-15

    Failure of passive transfer is a common problem in calves destined for veal production. At present it is unknown whether the risk for respiratory disease (BRD) or neonatal calf diarrhea (NCD) in the veal herd is associated with total immunoglobulin (Ig) and/or on the serostatus for respiratory pathogens measured at arrival. Therefore, the first objective of this prospective longitudinal cohort study was to determine associations between serum protein fractions as determined by routine electrophoresis (total protein, albumin, alpha-1 and -2 globulins, beta-globulins and Ig's) at arrival and BRD and NCD in the first 3 weeks of the production cycle. The second objective was to determine whether the serostatus (seropositive/seronegative) of seven respiratory pathogens (bovine respiratory syncytial virus (BRSV), parainfluenzavirus-3, bovine coronavirus (BCV), bovine herpesvirus-1, bovine viral diarrhea virus, Mannheimia haemolytica and Mycoplasma bovis) of these arrival serum samples could be associated with the risk of having BRD. The third objective was to determine which of the electrophoresis proteins and respiratory serostatuses were associated with average daily gain (ADG) in the study period. The study population consisted of 150 rosé veal calves housed in a single air-space. The study period ended at day 18 post arrival, when BRD incidence was judged to be too high to further postpone a group treatment. A Cox regression model was used to determine the effect of the studied protein fractions and antibodies on the time to BRD and NCD occurrence. The effect of the studied predictors on ADG was determined by linear regression. Calves with Ig levels under 7.5g/L had an increased BRD hazard (hazard ratio (HR)=1.9 (95% confidence interval (CI)=1.2-3.0)). NCD was only positively associated with the alpha-2 globulin concentration. Calves with a negative serostatus for BCV (HR=1.7 (95% CI=1.0-2.8)) or BRSV (HR=2.0 (95% CI=1.0-3.9)) had an increased BRD hazard. Average

  18. 金欣口服液对呼吸道合胞病毒肺炎大鼠模型TNF-α、分泌型IgA的影响%The Effects of Jinxin Oral Liquid on the Secretion of the TNF-α and SIgA in Pneumonia Rats Induced by Respiratory Syncytial Virus

    Institute of Scientific and Technical Information of China (English)

    陈超; 夏晨; 徐建亚; 汪受传

    2011-01-01

    Objective: To investigate the effects of Jinxin oral liquid on the secretion of the TNF-α in serum and SIgA in bronchoalveolar lavage fluid and intestinal fluid of the pneumonia rats induced by Respiratory Syncytial Viruses.Methods: 56 Rats were randomly divided into seven groups, the normal control group, the model control group, low-dosage, medium-dosage and hig-dosage of Jinxin oral liquid groups, pretreated group and Ribavirin treated group.Rats in model control group, low-dos-age, medium-dosage and hig-dosage of Jinxin oral liquid groups and Ribavirin treated group were treated with RSV use nasal drip method for three days, and then all the groups except the model control group were treated with Jinxin oral liquid or Ribavirin for seven days.At the end of the experiment, the rats were killed, and the blood samples and broncho alveolus lavage fluid and intestinal fluid were collected.The TNF-α in serum and SIgA in bronchoalveolar lavage fluid and intestinal fluid were measured by ELISA.Results: Compared with normal control group, the serum level of TNF-αin model control group was higer (P<0.01 ).The serum levels of TNF-αin the high and medium dosage of Jinxin oral liquid groups were increased, when compared with the model control group, moreover, the serum lelve of TNF-αin high dosage of Jinxin oral liquid group was increased more that compared with the Ribavirin treated group ( P<0.01 ).The lelves of SIgA in bronchoalveolar lavage fluid and intestinal fluid were increased in Jinxin oral liquid pretreated group and high dosage of Jinxin oral liquid group, besides, the lelve of SIgA in bronchoalveolar lavage fluid was significantly increased.Conclusion: Jinxin oral liquid can increase the lelves of TNF-αand SIgA, furthermore there is a certain dese-effeet relationship bewteen them.All in all, Jinxin orad liquid is an effective compound in treating infectous disease, such as the pneumonia induced by Respiratory Syncytial Viruses.%目的:探讨中药复

  19. 白藜芦醇对呼吸道合胞病毒感染小鼠肺部病毒滴度及其气道炎症的影响%Effect of resveratrol on pulmonary vurus titer and airway inflammation in mice infected with respiratory syncytial virus

    Institute of Scientific and Technical Information of China (English)

    臧娜; 谢晓虹; 邓昱; 李思敏; 倪科; 罗艳; 王莉佳; 刘恩梅

    2011-01-01

    Objective To study the effect of resveratrol (RES) on pulmonary virus titer and airway inflammation in mice infected with respiratory syncytial virus (RSV). Methods Twenty-four female BALB/c mice at the age of 6 -8 weeks, treated with intra-abdominal cyclophosphamide (CYP) at the dose of 100 mg/kg, were randomly divided into control group, RSV infection group, and RES treatment group (8 in each group). Five days after CYP treatment, a RES infection model was induced by intranasal drip of RES. One hour after RES infection, the mice received intraperitoneal injection of RES or inhaled it at the dose of 30mg/(kg ? D). Five days later, airway hyper-response (AHR) in lucid mice was detected. The mice were then killed to detect the pulmonary RSV titers in the lung, the number of cells in bronchoalevolar lavage fluid (BALF), inflammation in lung tissue and its score. Results The pulmonary RSV titer, the number of cells in BALF, the score of inflammation in lung tissue, and the airway AHR were significantly lower in RES treatment group than in RSV infection group (P <0. 01). However, no significant difference was observed between RES treatment group and control group. Conclusion Differenly administrated RES can relieve RSV-induced inflammation and AHR by reducing pulmonary titer and inhibiting RSV replication in vivo.%目的 研究白藜芦醇(resveratrol,RES)对呼吸道合胞病毒(respiratory syncytial virus,RSV)感染小鼠肺部病毒滴度及其所致气道炎症的影响。方法6~8周龄雌性BALB/c小鼠,环磷酰胺100 mg/kg腹腔注射后,随机分为对照组、RSV感染组、白藜芦醇腹腔注射组、白藜芦醇雾化组,每组8只。环磷酰胺处理5d后,给予RSV滴鼻建立RSV感染模型,并在RSV感染1h后给予白藜芦醇30 mg/(kg·d)腹腔注射和雾化吸入。5d后检测小鼠清醒状态下气道阻力,处死小鼠研究肺部RSV病毒滴度、肺泡灌洗液(BALF)中细胞计数、肺部病理组织炎症及评分。

  20. 呼吸道合胞病毒毛细支气管炎患儿血和痰中白三烯测定及临床意义%The blood and sputum levels of leukotriene in children with respiratory syncytial viral bronchiolitis

    Institute of Scientific and Technical Information of China (English)

    易阳; 钟闻燕; 熊建新; 钱金强; 虞斌; 涂国华; 姚圣连

    2011-01-01

    Objective To investigate the effects of leukotriene in children with respiratory syncytial (RSV)viral bronchiolitis.Methods The blood and sputum levels of Ieukotriene were detected in 33 cases diagnosed RSV bronchiolitis and 12 cases which were diagnosed pneumonia without RSV infection.Thirty-three cases of bronchiolitis were devided into mild-moderate group(n =22)and severe group(n =11)according to the lowell score.Results The blood and sputum levels of leukotriene in mild-moderate group,severe group,and pneumonia group were(76.96 ± 28.19)pg/ml,(103.53 ± 16.85)pg/ml,(18.14.± 7.49)pg/ml;(31.83 ± 19.14)pg/ml,(67.11 ± 15.11)pg/ml,(6.81 ± 2.90)pg/ml in acute period,and(36.04 ±16.38)pg/ml,(52.27 ± 17.03)pg/m l,(18.14 ± 7.49)pg/ml of serum in recovery period.There were significant differences among three groups(F =48.09,P < 0.001 ; F =15.50,P < 0.001 ; F =44.43,P <0.001).After treatment,the blood levels of leukotriene were significantly decreased,but were still higher than that of pneumonia group(P < 0.05).Conclusion The blood and sputum levels of leukotriene increase in children with RSV bronchiolitis,which is related with the severity of bronchiolitis.%目的 探讨呼吸道合胞病毒(respiratory syncytial virus,RSV)毛细支气管炎(毛支炎)患儿血、痰中白三烯C4(leukotriene C4,LTC4)水平的变化及临床意义.方法轻-中度毛支炎组22例,重度毛支炎组11例,另选择无喘息非RSV感染性肺炎患儿12例作为对照(肺炎组).采用双抗体夹心酶联免疫吸附试验测定血清和痰中LTC4水平,并进行对比分析.结果急性期轻-中度毛支炎组、重度毛支炎组、肺炎组血清LTC4水平分别为(76.96±28.19)pg/ml、(103.53±16.85)pg/ml、(18.14±7.49)pg/ml;痰中LTC4水平分别为(31.83±19.14)pg/ml、(67.11±15.11)pg/ml、(6.81±2.90)pg/ml;恢复期血清LTC4水平分别为(36.04±16.38)pg/ml、(52.27±17.03)pg/ml、(18.14±7.49)pg/ml,3组间差异有统计学意义(F=48.09,P<0.001;F=15.50,P

  1. Study on the Effect of Realgar Nanoparticles on Reducing the Respiratory Syncytial Virus Type A (RSV-A) Replication in Vitro%雄黄纳米微粒在细胞水平上抑制呼吸道合胞病毒复制的初步研究

    Institute of Scientific and Technical Information of China (English)

    程淼; 赵洪兰; 王成祥; 王惠芳; 张燕; 苟宝迪; 朱贞; 王明哲; 许文波

    2012-01-01

    This study was to establish a model to explore anti- RSV effect of different administration method of Chinese medicine realgar on respiratory syncytial virus type A (RSV-A) replication in Hep-2 cells. U-sing high-energy ball milling with distilled water to prepare realgar nanoparticles, the concentration of nanometer realgar was tested by molybdenum blue staining method and the size of realgar nanoparticles was tested on Nano Series. Cell culture with ribavirin as a positive control was applied to observe the effect of anti-respiratory syncytial virus type A replication through prevention, treatment or direct inactivation of three different drug administration methods. Realgar nano-particles was found to be a potential inhibitor of RSV-A in a concentration-dependent manner with the median toxic concentration(TC50) of 0. 649μg/mL in Hep-2 cell culture. The median inhibition concentration(IC50) was 0. 20μg/mL when drug was added before virus infection. The IC50 was 0.13μg/mL when drug was added after virus infection,and it was 0. 16μg/mL when the drug was mixed with virus and added. The therapeutic index(TI)was 3. 18,4. 99 and 4. 11,respectively. The results showed realgar nanoparticles could inhibit the replication of the RSV and inactivate the RSV in vitro.%建立呼吸道合胞病毒A型(RSV-A型)感染Hep-2细胞模型,通过预防、治疗及直接灭活三种不同给药方式,观察中药雄黄对RSV-A型感染Hep-2细胞病变(CPE)的抑制作用.用高能球磨机研磨双蒸水水飞处理制备雄黄纳米微粒,应用砷钼蓝染色法测定雄黄纳米微粒浓度并在Nano Series粒度测定仪上测定其粒度.以MTT法计算药物的半数中毒剂量(TCs0).通过三种不同给药方式即预防给药、治疗给药及直接灭活给药方式进行体外实验,以利巴韦林为阳性对照药,观察雄黄纳米微粒对RSV-A型感染Hep-2细胞病变所起的作用,并对药物的量效关系进行分析.雄黄纳米微粒TC50值为0.649 μg/mL

  2. Determinación de subtipos del virus respiratorio sincicial en muestras positivas por el virus, aisladas en el Hospital Nacional de Niños Detection of Human Respiratory Syncytial Virus subtypes A and B in hospitalized children in Costa Rica

    Directory of Open Access Journals (Sweden)

    Doris Mora

    2011-01-01

    Full Text Available Objetivo: El virus respiratorio sincicial (VRS es un pneumovirus de la familia Paramyxovridae, que causa enfermedad severa del tracto respiratorio inferior en neonatos y niños pequeños, especialmente en los primeros años de vida. Es responsable de constantes hospitalizaciones y visitas a los servicios de emergencias. Se han identificado dos subtipos: VRS-A y VRS-B, mediante anticuerpos monoclonales y técnicas moleculares. El objetivo de este estudio fue establecer por primera vez la circulación de ambos subtipos del VRS, en muestras positivas de niños hospitalizados durante el pico estacional de 2008, en el Hospital Nacional de Niños (HNN. Métodos: Se analizaron 49 muestras de aspirados nasofaríngeos de niños hospitalizados, de un total de 578, de las cuales 197 fueron previamente positivas para VRS por inmunofluorescencia directa. Se realizó cultivo celular, y un RT-PCR múltiple, estandarizado en el laboratorio, para detectar VRS-A y VRS-B. Resultados: La frecuencia del VRS fue del 34% en el HNN, para agosto y septiembre de 2008. De las 49 muestras analizadas por RT-PCR, 41 (84% fueron positivas, 34 (83% por el subtipo A y 7 (17% por el B; 8 fueron negativas. Ningún paciente presentó infección mixta y no hubo diferencia entre los síntomas, la edad o el origen geográfico de los niños. El cultivo fue positivo solo en el 30% de las muestras. Conclusión: La frecuencia del VRS para el periodo en estudio fue del 34% de las muestras analizadas en aspirados nasofaríngeos. Este es el primer reporte de la detección de los subtipos A y B del VRS, en una pequeña cohorte del HNN, confirmados por un RT-PCR múltiple estandarizado en el laboratorio.Aim: Respiratory syncytial virus (RSV a Pneumovirus belonging to Paramyxovridae family is a common cause of severe lower respiratory disease in neonates and young children especially in the first years of life. It causes frequent hospitalizations and visits to the emergency rooms. Utilizing

  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. Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with Bovine RSV and Mannheimia haemolytica

    Science.gov (United States)

    Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovi...

  5. Comparison of direct immunofluorescence, conventional cell culture and polymerase chain reaction techniques for detecting respiratory syncytial virus in nasopharyngeal aspirates from infants Comparação entre imunofluorescência direta, cultura convencional de células e reação em cadeia de polimerase para detectar vírus respiratório sincicial em lavados de nasofaringe de crianças

    Directory of Open Access Journals (Sweden)

    Alexanda Dias Reis

    2008-02-01

    Full Text Available A total of 316 samples of nasopharyngeal aspirate from infants up to two years of age with acute respiratory-tract illnesses were processed for detection of respiratory syncytial virus (RSV using three different techniques: viral isolation, direct immunofluorescence, and PCR. Of the samples, 36 (11.4% were positive for RSV, considering the three techniques. PCR was the most sensitive technique, providing positive findings in 35/316 (11.1% of the samples, followed by direct immunofluorescence (25/316, 7.9% and viral isolation (20/315, 6.3% (p Um total de 316 amostras de lavado de nasofaringe obtidas de crianças em acompanhamento ambulatorial com até dois anos de idade durante episódio de doença aguda do trato respiratório foram processadas para detecção do vírus sincicial respiratório (VSR utilizando três diferentes técnicas: isolamento viral, imunofluorescência direta e reação em cadeia por polimerase (RT-PCR. Destas amostras, 36 (11,4% foram positivas para o VSR. A RT-PCR foi a técnica mais sensível, com positividade em 35 (11,1% das amostras, seguindo-se a imunofluorescência direta (25/316, 7,9% e o isolamento viral (20/315, 6,3% (p < 0,001. Uma amostra foi positiva pela imunofluorescência e negativa pela RT-PCR, e 11/36 (31,4% foram positivas somente pela RT-PCR. Concluímos que a RT-PCR é mais sensível que a imunofluorescência e o isolamento viral para detecção do VRS em amostras de aspirado de nasofaringe de recém-nascidos e lactentes.

  6. 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...

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

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    2003-01-01

    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...

  8. Vitro experimental study of anti-respiratory syncytial virus effect on Jinxin Oral Liquid transitional ingredients of blood%金欣口服液血中移行成分体外抗呼吸道合胞病毒的研究

    Institute of Scientific and Technical Information of China (English)

    杜丽娜; 单进军; 徐建亚; 戴启刚; 汪受传

    2013-01-01

    Objective: To elucidate the substance basis of Jinxin Oral Liquid by analyze anti-respiratory syncytial virus (RSV) effect of the constituents in serum of rats oral adinistrated with Jinxin Oral Liquid. Methods: The effect of anti-RSV was evaluated with RSV infected human laryngeal epithelial cells(Hep-2) for transitional ingredients of quercetin, polydatin, baicalein, wogonin, isorhamnetin, physcion by cell culture technology and methyl thiazolyl tetrazolium(MTT) colorimetric assay detecting cell activity, as a positive control drug ribavirin, therapeutic index(TI) as an evaluating indicator. Results: Quercetin, Polydatin, Baicalein, Isorhamnetin, Physcion had a direct inactivation of RSV in infected Hep-2 cells, the TI was 12.78, 38.07, 28.93, 9.43, 1.58, respectively. Quercetin, Isorhamnetin had a therapeutic effect on RSV infection, the TI was 12.0, 4.25, respectively; Wogonin had a preventive effect, the TI was 1.57. Conclusion: Quercetin, Polydatin, Baicalein, Wogonin, Isorhamnetin and Physcion are the material basis for anti-virus in Jinxin Oral Liquid.%目的:通过研究金欣口服液血中移行成分的体外抗呼吸道合胞病毒(RSV)作用,明确金欣口服液作用的物质基础.方法:采用细胞培养技术,噻唑蓝(MTT)比色法检测细胞活性,以利巴韦林为阳性对照,观察金欣口服液血中移行成分槲皮素、虎杖苷、黄芩素、汉黄芩素、异鼠李素、大黄素甲醚在人喉癌上皮细胞(Hep-2)中对RSV的抑制作用,以治疗指数(TI)为评价指标.结果:在Hep-2细胞中槲皮素、虎杖苷、黄芩素、异鼠李素、大黄素甲醚对RSV具有直接灭活作用,TI分别为12.78、38.07、28.93、9.43、1.58,槲皮素、异鼠李素对RSV感染具有一定的治疗作用,TI分别为12.00、4.25,汉黄芩素对RSV感染有预防作用,TI为1.57.结论:槲皮素、虎杖苷、黄芩素、汉黄芩素、异鼠李素、大黄素甲醚是金欣口服液抗呼吸道合胞病毒的物质基础.

  9. Effect of Pentoxifylline on the Expression Level of TNF-α Gene Induced by Respiratory Syncytial Virus%己酮可可碱对呼吸道合胞病毒所致的TNF-α基因表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    彭毅; 陶晓南; 杨业金; 付薇; 向敏; 张瑞祥

    2000-01-01

    观察己酮可可碱(PTX)对呼吸道合胞病毒(RSV)所诱导的巨噬细胞肿瘤坏死因子(TNF-α)含量及TNFα mRNA表达水平的影响。收集Balb/c小鼠腹腔巨噬细胞,随机分成三组①对照组(NOR组);②感染组(RSV组):培养基中含有106pfu的RSV;③已酮可可碱组(PTX组):用RSV(106pfu)感染后,培养基中加入PTX(1 mg/ml);每组于RSV感染巨噬细胞20 h后,用ELISA法测定培养细胞上清中TNF-α含量的变化,同时用逆转录聚合酶链反应(RT-PCR)测定各组巨噬细胞TNF-α mRNA表达水平。结果表明:感染组中TNF-α mRNA表达水平与对照组相比明显增多。PTX组TNF-α mRNA的表达和感染组相比明显降低。TNF-α的含量也有相应的变化:与对照组比较,感染组明显升高(P<0.01);而PTX组与感染组比较明显下降(P<0.01)。认为PTX能抑制RSV所诱导的巨噬细胞TNF-α的基因表达,并减少TNF-α的产生。%The effect of pentoxifylline (PTX) on level of the TNF-α and expression of TNF-α mRNA induced by respiratory syncytial virus (RSV) were studied. Peritoneal macrophages were collected from Balb/c mice and randomly divided into three groups: control group (NOR group), RSV infecting group (RSV group), containing 106 pfu RSV in the culture medium, and PTX group wiht 1 mg/ml of PTX being added into the culture medium after RSV infection. Twenty h after the RSV infection, the mRNA expression level of TNF-α gene in the supernatant was detected by using RT-PCR and TNF-α protein level by using ELISA method, respectively. The results showed that the mRNA expression level of TNF-α gene was increased in the RSV group as compared with that in the NOR group, while it was obviously decreased in PTX group as compared with RSV group. Similar results were also obtained in the changes of TNF-α. It was suggested that PTX exerted an inhibitory effect on the expression of the TNF-α gene induced by RSVon the level of its mRNA and reduce

  10. 呼吸道合胞病毒感染诱导BALB/c鼠固有免疫细胞分泌 IL-33%Respiratory Syncytial Virus Infection Induced Excretion of IL-33 in Innate Immune Cells in BALB/c mice

    Institute of Scientific and Technical Information of China (English)

    戚菲菲; 王锐莹; 刘静; 曾胜; 刘北星

    2014-01-01

    IL-33 is a newly found cytokine;it plays an important role in virus infection induced airway inflammation reaction. It was found in the study that the level of IL-33 was significantly increased in the lungs of BALB/ c mice in-fected with respiratory syncytial virus(RSV). However,the immune cell types for IL-33 excretion after RSV infec-tion,especially the cell types of the innate immune cells,remain unknown so far. In this study,by isolating and cul-tivating alveolar macrophages and dendritic cells from BALB/ c mice,the change of IL-33 excretion level in innate im-mune cells after infected with RSV were tested and determined with ELISA and real-time PCR. The results showed that at 72 h after RSV infection,the expression of IL-33 mRNA level in the alveolar macrophages increased signifi-cantly. Meanwhile,the expression of IL-33 mRNA level in dendritic cells began to increase 24 h after the infection, and reached to a peak at 48 h after RSV infection. This study has confirmed that RSV infection induced BALB/ c mice innate immune cells to excrete IL-33,and proceed to medium-leading the occurrence and development of inflammation after the infection.%IL-33是新发现的细胞因子,在病毒感染所诱发的气道炎症反应中发挥重要作用。研究发现感染呼吸道合胞病毒的 BALB/ c 鼠肺组织内 IL-33水平明显升高。但 RSV 感染后分泌 IL-33的免疫细胞类型,尤其是感染早期分泌 IL-33的固有免疫细胞类型目前尚不清楚。通过分离培养 BALB/ c 鼠肺泡巨噬细胞及树突状细胞,采用 ELISA 及实时荧光定量 PCR 法检测上述固有免疫细胞 RSV 感染后 IL-33分泌水平的变化。结果显示,RSV 感染72 h 后 BALB/ c 鼠肺泡巨噬细胞 IL-33mRNA 水平明显升高,而树突状细胞 RSV 感染24 h 后 IL-33mRNA 水平开始上升,48 h 达峰值。研究证实 RSV 感染诱导 BALB/ c 鼠固有免疫细胞分泌 IL-33,进而介导感染后炎症的发生发展。

  11. 外源性IP-10对流感病毒及呼吸道合胞病毒感染小鼠肺病理学影响%The effect of exogenous IP-10 on mice's pulmonary pathology induced by influenza virus and respiratory syncytial virus

    Institute of Scientific and Technical Information of China (English)

    金红; 车海龙; 王冬; 赵月

    2011-01-01

    Objective To study the effect of γ interferon-inducible protein 10 (IP-10) on pulmonary pathological changes in mice infected with influenza virus (IV) or respiratory syncytial virus(RSV). Methods Pulmonary pathological changes in mice infected with IV or RSV after being administered IP-10 were compared with mice infected with IV or RSV alone, normal control and only IP-10 administration mice were set up. Results The mice infected with IV or RSV after receiving IP-10 developed severe pulmonary inflammation, mice infected with IV or RSV alone also developed interstitial pneumonia, but less serious than the mice infected with IV or RSV receiving IP-10, there were significant difference between the two respectively (t = - 12. 56;t = -5. 60, both P<0. 01). After being administered IP-10, mice infected with IV was more serious than the mice infected with RSV, there was significant difference in pathological scores of interstitial pneumonia (t = 7. 73, P<0. 01 ). Conclusion IP-1 0 is an important chemokine which has great effect on the severity of pneumonia caused by IV or RSV.%目的 研究γ干扰素诱导蛋白10(IP-10)对感染流感病毒或呼吸道合胞病毒(RSV)小鼠的肺部病理学变化的影响.方法 对单纯感染流感病毒或RSV以及注射重组小鼠IP-10后再感染流感病毒或RSV小鼠的肺病理学变化进行比较,同时设正常对照组和仅注射IP-10对照组.结果 注射IP-10后,感染流感病毒或RSV组小鼠出现严重肺部炎症,而单纯感染病毒组小鼠虽然也呈间质性肺炎表现,但病变程度远较前2组轻,差异具有高度显著性(t值分别为-12.56、-5.60,均P<0.01).注射IP-10后,感染流感病毒组小鼠肺炎重于RSV感染组,两组间质性肺炎病理评分比较,差异具有高度显著性(t=7.73,P<0.01).结论 IP-10对病毒所致小鼠肺部炎性病变,特别是对流感病毒性肺炎严重程度具有重要影响.

  12. Development and Application of TaqMan Probe Real-Time PCR Assay for Detection of Respiratory Syncytial Virus%呼吸道合胞病毒TaqMan探针实时定量RT-PCR检测方法的建立及应用

    Institute of Scientific and Technical Information of China (English)

    郑文芝; 张骞; 魏建民; 薛鹏浩; 王翔; 赵智慧; 郑丽舒

    2012-01-01

    目的:建立呼吸道合胞病毒(RSV)核酸特异、快速、敏感的TaqMan探针实时荧光定量PCR检测方法,并对临床样本进行检测.方法:比对编码RSV非编码蛋白的基因序列,选取其保守片段设计引物和探针,建立实时荧光定量RT-PCR检测方法,并与传统RT-PCR方法进行比较,分别对两者的灵敏性、特异性、重复性及临床样本检验的适用性进行评价.结果:所建立的实时荧光定量RT-PCR检测方法可用于RSV的特异性检测.相对于传统RT-PCR方法100拷贝/反应的检测灵敏度,实时荧光定量RT-PCR的检测灵敏度达到10拷贝/反应,检测范围为1010~101拷贝/反应,且具有良好的特异性和重复性.从169份临床呼吸道标本中检出RSV阳性40例,高于普通PCR方法(31/169).结论:建立了RSV的TaqMan探针实时定量PCR检测方法,并可用于临床鼻咽拭子样本的检测,在临床上具有较好的应用前景.%Objective: To develop a specific, rapid, sensitive TaqMan based real-time quantitative PCR assay for detection and quantitation of respiratory syncytial virus (RSV). Methods: The specific primers and fluorescence-labeled probe were designed according to the conservative gene sequence of RSV. Absolute viral copy was achieved through the standard curve. Subsequently, experiments were undertaken to assess specificity, sensitivity and reproducibility, then compared with conventional PCR using clinic specimen. Results: Compared with conventional RT-PCR 100 copies per reaction mixture, the sensitivity of this real-time RT-PCR assay was 10 copies per reaction and the detection limit was ranging from 1010 -101 copies per reaction. Moreover, this real-time RT-PCR assay showed a good specificity and reproducibility. Among 169 nasopharyngeal swab specimens, 40 specimens were identified positive for RSV using real-time RT-PCR, higher than that by conventional RT-PCR (31/ 169). Conclusion: A real-time RT-PCR assay for detection of RSV has been

  13. Cross protection of a Mannheimia haemolytica A1 Lkt-/Pasteurella multocida ΔhyaE bovine respiratory disease vaccine against experimental challenge with Mannheimia haemolytica A6 in calves.

    Science.gov (United States)

    Crouch, C F; LaFleur, R; Ramage, C; Reddick, D; Murray, J; Donachie, W; Francis, M J

    2012-03-16

    Bovine respiratory disease causes significant economic losses in both beef and dairy calf industries. Although multi-factorial in nature, the disease is characterized by an acute fibrinous lobar pneumonia typically associated with the isolation of Mannheimia haemolytica. M. haemolytica A1 and A6 are the two most commonly isolated serotypes from cattle, however, the majority of vaccines have not demonstrated cross-serotype protection. In the current study, the efficacy of a novel, attenuated live vaccine, containing both M. haemolytica serotype A1 and Pasteurella multocida, was evaluated in calves challenged with M. haemolytica serotype A6. Although the challenge was more severe than expected, vaccinated calves had reduced clinical scores, lower mortality, and significantly lower lung lesion scores compared to the placebo-vaccinated control group. The results demonstrate that vaccination with an attenuated live vaccine containing M. haemolytica serotype A1 can protect calves against clinical disease following challenge with M. haemolytica serotype A6.

  14. One year duration of immunity of the modified live bovine viral diarrhea virus type 1 and type 2 and bovine herpesvirus-1 fractions of Vista® Once SQ vaccine.

    Science.gov (United States)

    Purtle, Lisa; Mattick, Debra; Schneider, Corey; Smith, Linda; Xue, Wenzhi; Trigo, Emilio

    2016-03-18

    Three studies were performed to determine the duration of immunity of the bovine viral diarrhea virus type 1 and type 2 (BVDV-1 and BVDV-2) and bovine herpesvirus-1 (BHV-1) fractions of a commercially prepared modified-live vaccine. Vista® Once SQ (Vista®) vaccine contains five modified-live viruses, BVDV-1, BVDV-2, BHV-1, bovine respiratory syncytial virus, and bovine parainfluenza 3 virus, and two modified-live bacteria, Pasteurella multocida and Mannheimia haemolytica. For all three studies, calves were administered a single dose of vaccine or placebo vaccine subcutaneously, and were challenged with one of the three virulent viruses at least one year following vaccination. Calves were evaluated daily following challenge for clinical signs of disease associated with viral infection, nasal swab samples were evaluated for virus shedding, and serum was tested for neutralizing antibodies. Following the BVDV-1 and BVDV-2 challenges, whole blood was evaluated for white blood cell counts, and for the BVDV-2 study, whole blood was also evaluated for platelet counts. Calves vaccinated with BVDV type 1a, were protected from challenge with BVDV type 1b, and had significant reductions in clinical disease, fever, leukopenia, and virus shedding compared to control calves. Vaccinated calves in the BVDV-2 study were protected from clinical disease, mortality, fever, leukopenia, thrombocytopenia, and virus shedding compared to controls. Vaccinated calves in the BHV-1 study were protected from clinical disease and fever, and had significantly reduced duration of nasal virus shedding. These three studies demonstrated that a single administration of the Vista® vaccine to healthy calves induces protective immunity against BVDV-1, BVDV-2 and BHV-1 that lasts at least one year following vaccination.

  15. Rapid and generic identification of respiratory viruses with mass spectrometry - Poster

    NARCIS (Netherlands)

    Majchrzykiewicz-Koehorst, J.A.; Heikens, E.; Trip, H.; Hulst, A.G.; Jong, A.L. de; Viveen, M.C.; Sedee, N.J.A.; Plas, J. van der; Coenjaerts, F.E.J.; Paauw, A.

    2014-01-01

    Tested respiratory viruses: influenza A virus, respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), were successfully identified directly from crude cell cultures using liquid chromatography-tandem MS (LC-MS/MS). The identification was preceded with the simple, generic and fast sample

  16. RAPID DETECTION OF RESPIRATORY VIRUSES USING MIXTURES OF MONOCLONAL-ANTIBODIES ON SHELL VIAL CULTURES

    NARCIS (Netherlands)

    SCHIRM, J; LUIJT, DS; PASTOOR, GW; MANDEMA, JM; SCHRODER, FP

    1992-01-01

    Eleven hundred and thirty-three clinical specimens submitted to the laboratory for diagnosis of respiratory virus infections were tested by direct immunofluorescence (DIF) for respiratory syncytial virus (RSV), by shell vial culture, and by conventional cell culture. The shell vial cultures were sta

  17. Acute otitis media and respiratory virus infections.

    Science.gov (United States)

    Ruuskanen, O; Arola, M; Putto-Laurila, A; Mertsola, J; Meurman, O; Viljanen, M K; Halonen, P

    1989-02-01

    We studied the association of acute otitis media with different respiratory virus infections in a pediatric department on the basis of epidemics between 1980 and 1985. Altogether 4524 cases of acute otitis media were diagnosed. The diagnosis was confirmed by tympanocentesis in 3332 ears. Respiratory virus infection was diagnosed during the same period in 989 patients by detecting viral antigen in nasopharyngeal mucus. There was a significant correlation between acute otitis media and respiratory virus epidemics, especially respiratory syncytial virus epidemics. There was no significant correlation between outbreaks of other respiratory viruses and acute otitis media. Acute otitis media was diagnosed in 57% of respiratory syncytial virus, 35% of influenza A virus, 33% of parainfluenza type 3 virus, 30% of adenovirus, 28% of parainfluenza type 1 virus, 18% of influenza B virus and 10% of parainfluenza type 2 virus infections. These observations show a clear association of respiratory virus infections with acute otitis media. In this study on hospitalized children Haemophilus influenzae strains were the most common bacteriologic pathogens in middle ear fluid, occurring in 19% of cases. Streptococcus pneumoniae was present in 16% and Branhamella catarrhalis in 7% of cases. There was no association between specific viruses and bacteria observed in this study.

  18. 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.

  19. Dynamics of human respiratory virus-specific CD8+ T cell responses in blood and airways during episodes of common cold

    NARCIS (Netherlands)

    Heidema, Jojanneke; Rossen, John W A; Lukens, Michaël; Ketel, Marianne S; Scheltens, Eva; Kranendonk, Mariette E G; van Maren, Wendy W C; van Loon, Anton M; Otten, Henny G; Kimpen, Jan L L; van Bleek, Grada M

    2008-01-01

    We determined the dynamics of CD8(+) T cells specific for influenza virus and respiratory syncytial virus in blood and tracheostoma aspirates of children during the course of respiratory infections. We showed that during localized respiratory infections the ratio of activated effector CD8(+) T cells

  20. 呼吸道合胞病毒感染对豚鼠咳嗽相关气道功能及其神经递质的影响%Effects of respiratory syncytial virus infection on cough-related airway function and neurotransmitter in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    叶新民; 钟南山; 刘春丽; 陈如冲; 赵谨

    2011-01-01

    Objective To investigate the effects of respiratory syncytial virus (RSV) infection on cough-related airway function and neurotransmitter in guinea pigs and to explore the pathogenesis of cough after RSV infection. Methods Sixty SPF male guinea pigs were randomly divided into control group,asthma group and four RSV-infected groups (6,12,28 and 42 d group), ten in each group. Infected animals were inoculated by intranasal instillation of RSV suspension, Plethysmography was used to assess cough reflex sensitivity (CRS) and airway responsiveness (AR). Vanilloid receptor-1 (VR1) mRNA level was detected by real-time PCR. The protein expressions of VR1 and protein gene product-9.5 (PGP-9.5)were measured by immunohistochemistry. Results CRS in 6, 12, 28 and 42 d RSV-infected group [ (8. 00 ± 3. 86), (8. 70± 6.20 ), ( 7.60 ±4.40 ) and ( 6.70 ± 3. 71 ) CCnt] was higher than that in control group [(2. 50±1.43) CCnt,all P <0.05] and reached a peak in 12 d RSV-infected group ( P <0.01). AR to two high concentrations of methylocholine in 12 d RSV-infected group [( 1 069 ± 156 )%,( 1 846±285) %] was higher than that in control group (all P <0.05). VR1 mRNA level in 6,12,28 and 42 d RSV-infected group (1.57 ± 0.43,1.61 ±0. 47 and 1.68 ± 0. 56) was higher than that in control group (1.00±0.34, P <0.05), and remained at highest level in 28 d RSV-infected group. Compared with control group, VR1 protein expression in 28 d RSV-infected group and PGP-9.5 in 12 d RSV-infected group increased (all P <0. 05). Conclusions The increased CRS with increased AR in a certain degree is the feature of cough caused by RSV. The temporal and spatial variation of VR1 and PGP-9. 5 may be related to the pathogenesis of cough caused by RSV.%目的 观察呼吸道合胞病毒RSV(感染)对豚鼠咳嗽相关的气道功能及神经递质的影响,探讨病毒感染后咳嗽的发病机制.方法 雄性SPF级豚鼠60只,按数字随机法随机分成正常对照组、病毒感染组

  1. Expression of recombinant respiratory syncytial virus F protein in eukaryotic cells and establishment of ELISA for detectiing the protein%呼吸道合胞病毒F蛋白基因片段真核细胞表达纯化及其ELISA建立的研究

    Institute of Scientific and Technical Information of China (English)

    包洪; 刘爱忠; 尹文东; 李艳蕾; 于庭

    2011-01-01

    目的 表达纯化人呼吸道合胞病毒(HRSV)F蛋白基因片段,建立间接夹心酶联免疫吸附分析法(ELISA),为进一步大量表达F基因、构建基因工程疫苗和快速临床检测奠定基础.方法 逆转录并扩增F基因中的F1片段,连接到载体中,转染真核细胞,诱导并纯化重组F蛋白.将纯化重组F蛋白免疫小鼠制备抗体血清,并建立间接夹心ELISA.通过100份标本,应用"金标法"对所建立的方法 进行验证.结果 成功获得F基因中F.片段的扩增产物,筛选阳性克隆,得到相对分子质量为45000的大最表达蛋白.确定了间接夹心ELISA的最佳反应条件和工作浓度;鼠抗F1IgG最佳质量浓度为3.2μg/mL,样品最佳反应时间为37℃70min,酶标兔抗鼠IgG最佳工作浓度为1:6000.与"金标法"对比,阳性样品的变异系数为3.2%~8.6%,阴性样品的变异系数为5.1%~8.3%,均小于10.0%,表明该方法 有良好的重复性.结论 构建的重组真核细胞能够大量表达F蛋白,纯化的F蛋白具有很好的免疫原性,制备的抗体血清用于ELISA能够得到准确的检测结果.%Objective To express human respiratory syncytial virus(HRSV) F protein fragment in eukaryotic system and establish a double antihody sandwich enzyme-linked immunosorbent assay(ELISA) for detecting the protein. so as to lay the foundation for larger scale expression of the F protein, generation of genetic engineering vaccine, and quick detection of the disease in clinic.Methods The cDNA encoding HRSV F protein F, fragment amplified by RT-PCR was inserted into the expression vector and transformed into COS 27 cells. The recombinant protein was punfied after expression and was subsequently used to immunize rat for the Seneration of antiserum. Double antibody sandwich ELISA was established and verified with 100 specimens in comparison to "gold standard" method. Results An F gene F, fragment of 45 000 Daltons was successfully expressed in COS 27 cells. The optimal

  2. Study of Tanreqing on thymic stromal lymphopoietin secretion in human bronchial epithelial cell infected by respiratory syncytial virus in vitro%痰热清对呼吸道合胞病毒感染人支气管上皮细胞分泌胸腺基质淋巴细胞生成素作用的体外研究

    Institute of Scientific and Technical Information of China (English)

    蓝丹; 檀卫平; 陈环; 吴葆菁; 麦贤弟; 黄花荣

    2011-01-01

    Objective To study effects of traditional Chinese medicine Tanreqing injection on the secretion of thymic stromal lymphopoietin ( TSLP) in human bronchial epithelial cell infected by respiratory syncytial virus ( RSV) in vitro. Methods 1. Hep-2 cell lines were cultured in vitro and infected hy RSV . Then the infectious titer of RSV was determined by TCID 50 technique. We established a model of NHBE infected by RSV . 2. NHBE were infected with series RSV titers and in series incubated hours . The level of TSLP in the culture supernatants was determined by enzyme -linked immunosorbent assay ( ELISA) . 3. The effect of Tanreqing treatment on TSLP secretion was based on cell culture in vitro. The level of TSLP in three types of drug delivery (inculing precaution , direct deactivation and therapy ) were determined by ELISA. Results 1. The mRNA of RSV was detected in total RNA of NHBE infected by RSV with QPCR method , which demonstrated that a model of RSV infection in vitro was established succesfully. 2. The level of TSLP in NHBE cells supernatants infected by RSV significantly increased , compared with non-RSV. In the same postinoculation ( 12,24 ,48 ,72 ,96 , 120 h) , TSLP level increased obviously with raised RSV titers , compared with NHBE group ( P< 0. 05 ) . According to the same RSV titer( 10 , 50 , 100 , 500 , 1000 TCID50) , TSLP level increased statistically in series infection time , compared with 12 h group ( P < 0. 05 ) .3. The TSLP level of NHBE -RSV +Tanreqing group and NHBE -RSV + Ribavirin group were evidently lower than NHBE -RSV group in all detected point ( 12 , 24 ,48, 72 h) and in all drug deliveiy ways ( P < 0. 05 ) , especially in precaution way. TSLP level of NHBE-Tanreqing group are depressed than NHBE -Ribavirin group by precaution ( P < 0. 05 ) . Conclusions 1. TSLP secretion induced by RSV infection obviously increased which was related with raiseded RSV titer and infected duration . 2. Tanreqing injection inhibited TSLP secretion

  3. The variations and significance of IL-17 and IgE in infant with respiratory syncytial virus bronchiolitis%呼吸道合胞病毒毛细支气管炎患儿外周血IL-17和IgE水平变化及意义

    Institute of Scientific and Technical Information of China (English)

    陈霞; 曲书强

    2013-01-01

    Objective:Explore the variations of IL-17and IgE after respiratory syncytial virus infection and the relationship between IL-17and serum IgE.In order to provide new molecular basis in which the early prevention of RSV bronchiolitis transform to asthma in children.Method:Using enzyme hnked immunosorbent assay (ELISA) method to determine RSV antibody of children And so is divided into the RSV bronchiolitis group and non-RSV bronchiolitis group.Using enzyme linked immunosorbent assay (ELISA)method to determine IL-17 and serum IgE in 60 cases of children with bronchiolitis and 20 cases of healthy infants in plasma.useing spss to process date.Result:IL-17 in children with RSV bronchiolitis is 17.47 ± 1.30pg/mL,in non-RSV bronchiolitis group is 13.58 ±:0.89pg/mL and in the control group is 10.57 ±0.77 pg/mL.They have significant difference (P <0.05).IL-17 in RSV bronchiolitis group and in non-RSV bronchiolitis group have significant difference (P < 0.05).Serum IgE in children with RSV bronchiolitis is 84.28 ± 15.50IU/mL and in non-RSV bronchiolitis group is73.14 ± 11.70 IU/mL,in the control group is 14.68 ± 1.58IU/mL.They have significant difference (P < 0,05).But serum IgE in RSV bronchiolitis group and in non-RSV bronchiolitis group does not have difference (P >0.05).And IL-17 and IgE in serum in children wtith RSV bronchiolitis correlate.Conclusion:1.IL-17 may participat in the RSV infection immune mechanism.2.Children with bronchiolitis may exist similar immune mechanisms to athma,serum IgE may not be associated with specific pathogens.3.Children with bronchitis after RSV infection IL-17may promote the generation.of serum IgE.%目的 探讨呼吸道合胞病毒感染后血浆IL-17和血清IgE水平变化以及IL-17与IgE的关系,以期为早期预防RSV毛细支气管炎向儿童哮喘转化提供新的分子学依据.方法 利用酶联免疫吸附试验(ELISA)测定60例毛细支气管炎患儿血清RSV抗体,分为RSV毛支组和非RSV毛支组,并

  4. 利巴韦林对呼吸道合胞病毒感染哮喘加重小鼠胸腺基质淋巴细胞生成素分泌的影响%Effect of ribavirin upon secretion of thymic stromal lymphopoietin in respiratory syncytial virus-induced asthma exacerbation of mice

    Institute of Scientific and Technical Information of China (English)

    夏虎; 蔡绍曦; 佟万成; 骆利敏; 于化鹏

    2009-01-01

    Objective To investigate the role of ribavirin (RIB) in treating respiratory syncytial virus (RSV)-induced asthma exacerbation of mice.Methods (1)Cell experiment: 32 flasks of human airway epithelial cell 16HBEs were randomly divided into four groups: RSV group, RSV/RIB group, RIB group and control group. 16HBEs were infected with RSV at a multiplicity of infection (MOI) of 2. RIB 50 μg/ml was added in culture medium and Western blot used to detect the production of thymic stromal lymphopoietin (TSLP) protein; (2) Animal experiment: 32 female BALB/c mice were randomly divided into four groups: Ovalbumin (OVA) group, OVA/RSV group, OVA/RSV /RIB group and control group. Mice were sensitized by OVA and stimulated with nebulized OVA. RSV was inoculated into murine nasal cavity and RIB 10 mg/kg intramuscularly administered. BUXCO noninvasive murine lung function detection instrument was used to examine the airway response to metacholine; ELISA was used to detect IL-4, IL-5, IL-13 and IFN-γ in murine serum and TSLP in supernatants of bronchoalveolar lavage fluid (BALF);murine lung specimens were stained with HE to observe inflammation and immunohistochemical technique was employed to observe the production of TSLP in murine airway epithelial cells.Results The cell experiment demonstrated the productions of TSLP protein in RSV group, RSV/RIB group, RIB group and control group were 1.97±0.22, 1.16±0.19, 0.99±0.17 and 0.89±0.08 respectively, and the production of TSLP in RSV/RIB group was lower than that in RSV group(P<0.01). The animal experiment demonstrated that the murine airway responsiveness in RSV/OVA/RIB group was lower than that in OVA/RSV group(P<0.01). The levels of IL-4 [(109.7±41.9) pg/ml], IL-5 [(220.8±30.9) pg/ml], IFN-γ [(13.0±3.4) pg/ml] in murine serum and TSLP [(1945±82) pg/ml] in BALF of RSV/OVA/RIB group were significantly lower than those in OVA/RSV group [(274.2±103.7), (293.3±46.1), (30.1±5.7) and (2127±46) pg/ml respectively, all

  5. Effects of on-arrival versus delayed clostridial or modified live respiratory vaccinations on health, performance, bovine viral diarrhea virus type I titers, and stress and immune measures of newly received beef calves.

    Science.gov (United States)

    Richeson, J T; Kegley, E B; Gadberry, M S; Beck, P A; Powell, J G; Jones, C A

    2009-07-01

    Stress, commonly associated with weaning, marketing, and shipment of feeder cattle, can compromise immune function, and vaccine administration during immunosuppression may reduce vaccine efficacy and calf growth. Four treatments were compared in a 2 x 2 factorial arrangement to evaluate the effect of on-arrival (d 0) vs. delayed (d 14) administration of clostridial (CLOS) and respiratory (RESP) vaccines on health, performance, bovine viral diarrhea virus (BVDV) antibody titers, and physiological immune measurements of high-risk, newly received calves. Crossbred bull and steer calves (n = 263) were weighed (239 +/- 1.2 kg), stratified by sex, and randomly assigned to vaccination treatment: 1) arrival CLOS, arrival RESP (ACAR); 2) arrival CLOS, delayed RESP (ACDR); 3) delayed CLOS, arrival RESP (DCAR); and 4) delayed CLOS, delayed RESP (DCDR). Body weight and blood samples were collected on d 0, 14, 28, 42, and 56. Average daily gain did not differ (P > or = 0.34), averaging 0.98, 0.93, 0.95, and 0.91 kg/d for ACAR, ACDR, DCAR, and DCDR, respectively, for the entire 56-d trial. Vaccination timing did not affect morbidity (P > or = 0.23); however, there tended to be a CLOS timing effect (P = 0.07) and RESP timing effect (P = 0.09) on days to initial bovine respiratory disease (BRD) treatment. Average days to initial BRD treatment were less for ACAR (6 +/- 0.8 d) compared with DCDR (8 +/- 0.8 d; P = 0.01). Greater white blood cell counts were observed for DCDR than ACDR (P = 0.01), with ACAR and DCAR being intermediate. Serum cortisol concentrations were greater on d 0 than d 14 (P < 0.01) or d 28 (P = 0.01) but no treatment x day interaction (P = 0.21) was observed. Timing of RESP administration affected (P = 0.001) serum BVDV type I titers, with greater (P < 0.01) levels in calves receiving RESP vaccine on arrival. Delaying CLOS or RESP vaccination did not affect BW gain or morbidity in high risk, newly received stocker calves. Calves administered RESP vaccine on d 0

  6. 布地奈德吸入治疗呼吸道合胞病毒或鼻病毒感染所致婴幼儿第一次喘息的疗效分析%Analysis on the curative effect of budesonide inhalation in treatment of first infantile wheezing induced by respiratory syncytial virus infection or rhinovirus infection

    Institute of Scientific and Technical Information of China (English)

    夏煜; 李晓狄; 季正华

    2011-01-01

    Objective: To explore the curative effect of budesonide inhalation in treatment of first infantile wheezing induced by respiratory syncytial virus ( RSV) infection or rhinovirus (RV) infection. Methods; 212 infants with the first mild - moderate onset of wheezing hospitalized in asthma center of children hospital affiliated to Suzhou university from May 2004 to May 2006, then they were divided into treatment group and control group, the infants in control group were treated with inhalation of ventolin atomized liquid by a air pressure pump; the infants in treatment group were treated with budesonide inhalation on the basis of inhalation of ventolin atomized liquid. Direct im-munofluorescent method was used to detect RSV, adenovirus (ADV), influenza virus (IFV) and parainfluenza virus (PIV) in fresh sputum samples. RT - PCR was used to detect RV gene in the samples. Allergen screening test was conducted with UnicaplOO luciferase system. The birth history and family history of atopic diseases of the infants were collected. The average hospitalization times of simple RSV - infected infants or simple RV - infected infants in treatment group and control group were compared; at the same time, the average hospitalization times of simple RSV - infected infants and simple RV - infected infants were compared; the average hospitalization times of simple RV - infected infants in treatment group and control group were compared; the average hospitalization times of simple RSV - infected infants in treatment group and control group were compared. Results: The average hospitalization times of simple RSV - infected infants or simple RV - infected infants in treatment group and control group were (6. 71 ± 1. 79) days and (7. 25 ± 1. 64) days, respectively, there was no significant difference between the two groups (P > 0. 05) . The average hospitalization times of simple RSV - infected infants and simple RV - infected infants were (7. 25 ± 1. 86) days and (6. 64 ± 1. 54) days

  7. 呼吸道合胞病毒感染后气道上皮细胞Toll样受体4的表达及其功能%Toll-like receptor 4 expression and function of respiratory syncytial virus-infected airway epithelial cells

    Institute of Scientific and Technical Information of China (English)

    刘恩梅; 杨锡强; 罗嘉慧; 李欣; 谢晓虹; 王莉佳; 刘伟; 徐文飞

    2008-01-01

    after respiratory syncytial virus(RSV)infection and to explore the mechanisms of RSV-induced airway inflammation.Methods 9HTEo-human tracheal epithelial cell line was infected by RSV(MOI=10),and TLRl-10 mRNA were detected by RT-PCR assay at 3 h post RSV infection.TLR4 mRNA was detected by real time Q-PCR assay at 3 h,6 h and 9 h post RSV infection,and TLR4 protein expression and cell apoptosis were determined by flow cytometry at 24 h post RSV infection.IL-8 in supernatant was detected by ELISA after RSV-infected cells exposed to lipopolysaccharide(LPS).A normal control group and a RSV infection group were set up for the RT-PCR and flow cytometry experiments,and the data were analyzed by paried t test using GraphPad 4.0 software.A normal group,a RSV group and a UV-inactivated RSV group were set up for the real time Q-PCR,experiments,and the data were analyzedby Kruskal-Wallis test.The ELISA experiments were divided into 4 groups including a normal control.a RSV,a LPS stimulation,and a RSV plus LPS co-stimulation groups,and the data were analyzed by Oneway ANOVA test.Results (1)TLR2-10 mRNA level was significantly up-regulated(t value of TLR2-10:3.49~14.47,P<0.05),especially TLR-2,6 enhanced expression,compared with the normal epithelial cells.Real time Q-PCR assay showed that TLR4 mRNA started to increase at 3hr(Kruskal-Wallis test valne=8.82,P<0.05,n=6)and significantly elevated at 9 hour(Kruskal-Wallis test value=6.62,P<0.05,n=6).UV inactivated-RSV had no effect on the TLR4 mRNA level.(2)Flow cytometry showed that membrane TLR4 mean fluorescence intensity(MFI)increased(RSV:1.27±0.48,normal:0.97±0.25;t=2.39,P>0.05,n=10)while cytoplasmic TLR4 MFI simultaneously decreased(RSV:3.08±1.38,normal:3.36±1.31,t:2.92,P=0.225,n=10).Percentage of membrane TLR4-positive cells was higher in RSV infected population[RSV:(11.99±7.74)%,normal:(1.16±0.47)%,Mann-Whitneyt t value=0.001,P<0.01,n=8],most(93.32±1.7)%of which were Annexin V positive.IL-8 was significantly

  8. Risk factors for bovine respiratory disease in Australian feedlot cattle: use of a causal diagram-informed approach to estimate effects of animal mixing and movements before feedlot entry.

    Science.gov (United States)

    Hay, K E; Barnes, T S; Morton, J M; Clements, A C A; Mahony, T J

    2014-11-01

    A nationwide longitudinal study was conducted to investigate risk factors for bovine respiratory disease (BRD) in cattle in Australian feedlots. After induction (processing), cattle were placed in feedlot pens (cohorts) and monitored for occurrence of BRD over the first 50 days on feed. Data from a national cattle movement database were used to derive variables describing mixing of animals with cattle from other farms, numbers of animals in groups before arrival at the feedlot, exposure of animals to saleyards before arrival at the feedlot, and the timing and duration of the animal's move to the vicinity of the feedlot. Total and direct effects for each risk factor were estimated using a causal diagram-informed process to determine covariates to include in four-level Bayesian logistic regression models. Mixing, group size and timing of the animal's move to the feedlot were important predictors of BRD. Animals not mixed with cattle from other farms prior to 12 days before induction and then exposed to a high level of mixing (≥4 groups of animals mixed) had the highest risk of developing BRD (OR 3.7) compared to animals mixed at least 4 weeks before induction with less than 4 groups forming the cohort. Animals in groups formed at least 13 days before induction comprising 100 or more (OR 0.5) or 50-99 (OR 0.8) were at reduced risk compared to those in groups of less than 50 cattle. Animals moved to the vicinity of the feedlot at least 27 days before induction were at reduced risk (OR 0.4) compared to cattle undergoing short-haul transportation (factors could potentially be used to inform management decisions to reduce the risk of BRD in feedlot cattle.

  9. Detection of respiratory virus antigens in nasopharyngeal secretions from patients with acute respiratory disease by radio-immunoassay and tissue culture isolation.

    Science.gov (United States)

    Ehrlicher, L; Hoffmann, H G; Habermehl, K O

    1984-01-01

    An investigation was made of the sensitivity and specificity of four-layer radio-immunoassays (RIA) in the detection of adenovirus, respiratory syncytial virus, influenza virus types A and B, as well as para-influenza virus types 1, 2 and 3 from nasopharyngeal aspirates of 146 patients with acute respiratory disease. The sensitivity of RIA was comparable with that of tissue culture isolation if the total number of positives is considered. The difference may have been caused both by a higher efficiency of the RIA for detection of inactivated or non-cultivable agents and by a higher efficiency of tissue culture methods if the samples contained only small amounts of antigen. Differences between the two antigen detection systems were found in particular with respiratory syncytial virus and influenza B virus. At present, the use of tissue culture isolation together with RIA is the optimal routine laboratory procedure for the diagnosis of respiratory infections.

  10. The Etiological Structure of Acute Respiratory Diseases in the Years 2009—2013 in Children of Voronezh

    Directory of Open Access Journals (Sweden)

    S. P. Kokoreva

    2015-01-01

    Full Text Available The analysis of the etiology of acute respiratory infections was carried out in 865 children hospitalized to a hospital infection in the ears 2009—2013. It was found that respiratory viruses dominated in the etiological structure of acute respiratory infections of children, with a leading position in the number of revised survey diagnoses in different years of observation occupied influenza, but in recent years there is a growth trend of respiratory syncytial virus infection. The most pronounced seasonality of hospitalized children to help in the verification of the diagnosis, there was just the influenza, and mycoplasma infection. Children of preschool and school age with influenza and micoplasma infections are hospitalized more often, while for respiratory diseases other etiology, especially with respiratory syncytial virus infection children up to 3 years are hospitalized.

  11. Respiratory viruses in children hospitalized for acute lower respiratory tract infection in Ghana

    Directory of Open Access Journals (Sweden)

    Kwofie Theophilus B

    2012-04-01

    Full Text Available Abstract Background Acute respiratory tract infections are one of the major causes of morbidity and mortality among young children in developing countries. Information on the viral aetiology of acute respiratory infections in developing countries is very limited. The study was done to identify viruses associated with acute lower respiratory tract infection among children less than 5 years. Method Nasopharyngeal samples and blood cultures were collected from children less than 5 years who have been hospitalized for acute lower respiratory tract infection. Viruses and bacteria were identified using Reverse Transcriptase Real-Time Polymerase Chain Reaction and conventional biochemical techniques. Results Out of 128 patients recruited, 33(25.88%%, 95%CI: 18.5% to 34.2% were positive for one or more viruses. Respiratory Syncytial Virus (RSV was detected in 18(14.1%, 95%CI: 8.5% to 21.3% patients followed by Adenoviruses (AdV in 13(10.2%, 95%CI: 5.5% to 16.7%, Parainfluenza (PIV type: 1, 2, 3 in 4(3.1%, 95%CI: 0.9% to 7.8% and influenza B viruses in 1(0.8%, 95%CI: 0.0 to 4.3. Concomitant viral and bacterial co-infection occurred in two patients. There were no detectable significant differences in the clinical signs, symptoms and severity for the various pathogens isolated. A total of 61.1% (22/36 of positive viruses were detected during the rainy season and Respiratory Syncytial Virus was the most predominant. Conclusion The study has demonstrated an important burden of respiratory viruses as major causes of childhood acute respiratory infection in a tertiary health institution in Ghana. The data addresses a need for more studies on viral associated respiratory tract infection.

  12. Correlação entre mediadores inflamatórios na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior por vírus sincicial respiratório e a gravidade da doença Correlation between inflammatory mediators in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection caused by respiratory syncytial virus and disease severity

    Directory of Open Access Journals (Sweden)

    Renata Amato Vieira

    2010-02-01

    Full Text Available OBJETIVO: Avaliar se as concentrações dos mediadores inflamatórios (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 e IL-10 na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior (ITRI por vírus sincicial respiratório (VSR apresentam correlação com os marcadores clínicos de gravidade da doença. MÉTODOS: Entre julho de 2004 e dezembro de 2005, 30 crianças com idade inferior a três meses, diagnosticadas com ITRI por VSR e admitidas em uma UTI neonatal foram incluídas neste estudo. RESULTADOS: Houve uma correlação positiva significante entre a gravidade da doença na admissão hospitalar, determinada por um sistema de escore clínico modificado, e as concentrações de sICAM-1 e de IL-10 na secreção nasofaríngea e de IL-6 no soro dos pacientes. Houve também uma correlação positiva significante entre a concentração de IL-6 no soro e o tempo de oxigenoterapia e a duração da internação. CONCLUSÕES: As concentrações de sICAM-1 e IL-10 na secreção nasofaríngea e de IL-6 no soro determinadas na admissão poderiam ser usadas como marcadores de gravidade da ITRI por VSR. Os níveis de IL-6 determinados no soro na admissão também poderiam ser usados para predizer o prolongamento da oxigenoterapia e da duração da internação.OBJECTIVE: To determine whether the concentrations of inflammatory mediators (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 and IL-10 in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection (LRTI caused by respiratory syncytial virus (RSV correlate with the clinical markers of disease severity. METHODS: Between July of 2004 and December of 2005, 30 children less than three months of age, diagnosed with LRTI caused by RSV and admitted to a neonatal ICU, were included in this study. RESULTS: The severity of disease at hospital admission, as determined with a

  13. Mechanisms involved with immune hyperresponsiveness in newborns infected with respiratory viruses

    NARCIS (Netherlands)

    Stoppelenburg, A.J.

    2014-01-01

    Acute infection with respiratory syncytial virus (RSV) generally occurs during the first year of life. Approximately 1% of all infants is hospitalized for RSV bronchiolitis, of which 10% requires intensive care. RSV bronchiolitis is hallmarked by exaggerated mucus production and neutrophil infiltrat

  14. Association between respiratory infections in early life and later asthma is independent of virus type

    DEFF Research Database (Denmark)

    Bønnelykke, Klaus; Vissing, Nadja Hawwa; Sevelsted, Astrid;

    2015-01-01

    (respiratory syncytial virus, rhinoviruses, other picornaviruses, coronaviruses 229E and OC43, parainfluenza viruses 1-3, influenza viruses AH1, AH3, and B, human metapneumovirus, adenoviruses, and bocavirus) and 3 pathogenic airway bacteria (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella...

  15. 呼吸道合胞病毒毛细支气管炎患儿外周血CD4+CD25+调节性T细胞与Th17细胞功能变化及意义%Changes and the clinical significance of CD4+ CD25+ regulatory T cells and Th17 cells in peripheral blood of infants with respiratory syncytial virus bronchiolitis

    Institute of Scientific and Technical Information of China (English)

    李宾; 吴福玲; 冯学斌; 孙大康; 崔晴晴; 赵志旭

    2012-01-01

    AIM: To observe the percentages of CD4 + CD25+ regulatory T cells (Tregs) and Thl7 cells and the levels of IL-10, TGF-p and IL-17 in peripheral blood of infants with respiratory syncytial virus ( RSV) bronchiolitis. The relationship between above cells, cytokines and RSV bronchiolitis was determined. METHODS: Thirty-three infants with RSV bronchiolitis, twenty-eight infants with non-RSV pneumonia and twenty-six healthy infants were enrolled. The percentages of Tregs and Thl7 cells in peripheral blood were detected by flow cytometer (FCM), and the levels of IL-10, TGF-pand IL-17 in plasma were determined by ELISA. RESULTS: The percentage of Tregs and the levels of IL-10 and TGF-pin infants with RSV bronchiolitis were significantly lower than those in infants with non-RSV pneumonia and healthy infants ( P < 0. 05), while the percentage of Thl7 cells and the level of IL-17 in infants with RSV bronchiolitis were significantly higher than those in infants with non-RSV pneumonia and healthy infants ( P < 0. 05). CONCLUSION: The imbalance between Tregs and Thl7 cells in peripheral blood of infants with RSV bronchiolitis may be one of the pathogenesis of RSV bronchiolitis.%目的:探讨呼吸道合胞病毒(RSV)毛细支气管炎患儿外周血CD4+ CD25+调节性T细胞和Th17细胞及其分泌细胞因子IL-10、TGF-β、IL-17水平变化与RSV毛细支气管炎发病的关系.方法:收集2010-09/2011-04在滨州医学院附属医院儿科住院的33例RSV毛细支气管炎患儿、28例做为阳性对照的非RSV感染性肺炎患儿(肺炎组)及26例正常对照组的健康体检儿外周血,采用流式细胞术(FCM)检测外周血CD4+ CD25+调节性T细胞、Th17细胞百分率,酶联免疫吸附(ELISA)法检测血浆IL-10、TGF-β、IL-17的水平.结果:RSV毛细支气管炎患儿外周血CD4+ CD25+调节性T细胞、IL-10、TGF-β水平显著低于肺炎患儿及健康体检儿(P<0.05),而Th17、IL-17水平则显著高于肺炎患儿与健康体检儿(P<0

  16. Sequence analysis of a bovine rhinovirus type 1 strain RS3x

    Science.gov (United States)

    Bovine rhinoviruses, known to cause clinical and subclinical upper respiratory infections in bovines worldwide, include three serotypes. Bovine rhinovirus (BRV) 1, 2 and 3 were originally classified as tentative members of the genus Rhinovirus (family Picornaviridae), however, in 2008 this genus was...

  17. Detection of respiratory viruses and the associated chemokine responses in serious acute respiratory illness

    Science.gov (United States)

    Sumino, Kaharu C.; Walter, Michael J.; Mikols, Cassandra L.; Thompson, Samantha A.; Gaudreault-Keener, Monique; Arens, Max. Q.; Agapov, Eugene; Hormozdi, David; Gaynor, Anne M.; Holtzman, Michael J.; Storch, Gregory A.

    2010-01-01

    Background A specific diagnosis of a lower respiratory viral infection is often difficult despite frequent clinical suspicion. This low diagnostic yield may be improved by use of sensitive detection methods and biomarkers. Methods We investigated the prevalence, clinical predictors and inflammatory mediator profile of respiratory viral infection in serious acute respiratory illness. Sequential bronchoalveolar lavage (BAL) fluids from all patients hospitalized with acute respiratory illness over 12 months (n=283) were tested for the presence of 17 respiratory viruses by multiplex PCR assay and for newly-discovered respiratory viruses (bocavirus, WU and KI polyomaviruses) by single-target PCR. BAL samples also underwent conventional testing (direct immunoflorescence and viral culture) for respiratory virus at the clinician’s discretion. 27 inflammatory mediators were measured in subset of the patients (n=64) using a multiplex immunoassay. Results We detected 39 respiratory viruses in 37 (13.1% of total) patients by molecular testing, including rhinovirus (n=13), influenza virus (n=8), respiratory syncytial virus (n=6), human metapneumovirus (n=3), coronavirus NL63 (n=2), parainfluenza virus (n=2), adenovirus (n=1), and newly-discovered viruses (n=4). Molecular methods were 3.8-fold more sensitive than conventional methods. Clinical characteristics alone were insufficient to separate patients with and without respiratory virus. The presence of respiratory virus was associated with increased levels of interferon-γ-inducible protein 10 (IP -10)(p<0.001) and eotaxin-1 (p=0.017) in BAL. Conclusions Respiratory viruses can be found in patients with serious acute respiratory illness by use of PCR assays more frequently than previously appreciated. IP-10 may be a useful biomarker for respiratory viral infection. PMID:20627924

  18. ETIOLOGICAL STRUCTURE OF VIRAL RESPIRATORY DISEASES IN ADULT PATIENTS WITH BRONCHIAL ASTHMA EXACERBATION AND CHRONICAL BRONCHIOLITIS OBLITERANS

    Directory of Open Access Journals (Sweden)

    V. Z. Krivitskaya

    2015-01-01

    Full Text Available Exacerbation of bronchial asthma (BA and common deterioration of health during chronic bronchiolitis obliterans (ChBO are associated with viral infections in adults in 64 and 83% respectively. Mixed virus-viral associations were shown in 21–25% of cases. Respiratory syncytial infections were diagnosed with the highest frequency (50% in patients with BA. Influenza A(H1N1pdm09 and adenoviral infections dominated in persons with ChBO in 50 and 42% of cases, respectively. Response of virus-specific IgG in patients with BA and ChBO indicates the acute course of influenza A(H1N1pdm09 (63% of seroconversions. There were no reactions of IgG which is specific to respiratory syncytial virus in 75% of cases and to adenovirus in 83% of cases, that is the risk factor for occurrence of latent/persistent infection. Presence of structural components of respiratory syncytial virus in the upper respiratory tract had been revealed in three patients with asthma within at least 21–28 days. Respiratory syncytial viral infections and pandemic influenza A(H1N1 pdm09 in patients with BA and ChBO are characterized by the presence of an allergic component, which is indicated by the high levels of virus-specific IgE in blood. An adenoviral infection, in contrast, has no such peculiarity. 

  19. 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.

  20. 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.

  1. The yolk syncytial layer in early zebrafish development.

    Science.gov (United States)

    Carvalho, Lara; Heisenberg, Carl-Philipp

    2010-10-01

    The yolk syncytial layer (YSL) plays crucial roles in early zebrafish development. The YSL is a transient extra-embryonic syncytial tissue that forms during early cleavage stages and persists until larval stages. During gastrulation, the YSL undergoes highly dynamic movements, which are tightly coordinated with the movements of the overlying germ layer progenitor cells, and has critical functions in cell fate specification and morphogenesis of the early germ layers. Movement coordination between the YSL and blastoderm cells is dependent on contact between these tissues, and is probably required for the patterning and morphogenetic function of the YSL. In this review, we will discuss recent advances in elucidating the molecular and cellular mechanisms underlying the YSL morphogenesis and movement coordination between the YSL and blastoderm during early development.

  2. RESPIRATORY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    10.1 Respiratory failure2003068 Evaluation of non-invasive ventilation in a-cute respiratory failure with chronic obstructive pulmonary disease. GU Jianyong(顾俭勇), et al. Dept E-mergen, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Shanghai J Med 2002; 25 (12): 741 - 743.Objective:To observe the effect of non-invasive venti-lation(NIV) in acute respiratory failure with chronic

  3. Effects of acute respiratory virus infection upon tracheal mucous transport

    Energy Technology Data Exchange (ETDEWEB)

    Gerrard, C.S.; Levandowski, R.A.; Gerrity, T.R.; Yeates, D.B.; Klein, E.

    Tracheal mucous velocity was measured in 13 healthy non-smokers using an aerosol labelled with /sup 99m/Tc and a multidetector probe during respiratory virus infections. The movement of boluses of tracheal mucous were either absent or reduced in number in five subjects with myxovirus infection (four influenza and one respiratory syncytial virus) within 48 hr of the onset of symptoms and in four subjects 1 wk later. One subject with influenza still had reduced bolus formation 12-16 wk after infection. Frequent coughing was a feature of those subjects with absent tracheal boluses. In contrast, four subjects with rhinovirus infection had normal tracheal mucous velocity at 48 hr after the onset of symptoms (4.1 +/- 1.3 mm/min). Tracheal mucous velocity was also normal (4.6 +/- 1.1 mm/min) in four subjects in whom no specific viral agent could be defined but had typical symptomatology of respiratory viral infection. During health tracheal mucous velocity was normal (4.8 +/- 1.6 mm/min) in the eleven subjects who had measurements made. Disturbances in tracheal mucous transport during virus infection appear to depend upon the type of virus and are most severe in influenza A and respiratory syncytial virus infection.

  4. Multiscale diffusion in the mitotic Drosophila melanogaster syncytial blastoderm

    OpenAIRE

    2012-01-01

    Despite the fundamental importance of diffusion for embryonic morphogen gradient formation in the early Drosophila melanogaster embryo, there remains controversy regarding both the extent and the rate of diffusion of well-characterized morphogens. Furthermore, the recent observation of diffusional “compartmentalization” has suggested that diffusion may in fact be nonideal and mediated by an as-yet-unidentified mechanism. Here, we characterize the effects of the geometry of the early syncytial...

  5. 77 FR 29914 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Science.gov (United States)

    2012-05-21

    ... RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products AGENCY... live bovines and products derived from bovines with regard to bovine spongiform encephalopathy. This... with regard to bovine spongiform encephalopathy. Comments on the proposed rule were required to......

  6. Review of Non-Bacterial Infections in Respiratory Medicine: Viral Pneumonia.

    Science.gov (United States)

    Galván, José María; Rajas, Olga; Aspa, Javier

    2015-11-01

    Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia.

  7. Control of convergent yolk syncytial layer nuclear movement in zebrafish.

    Science.gov (United States)

    Carvalho, Lara; Stühmer, Jan; Bois, Justin S; Kalaidzidis, Yannis; Lecaudey, Virginie; Heisenberg, Carl-Philipp

    2009-04-01

    Nuclear movements play an essential role in metazoan development. Although the intracellular transport mechanisms underlying nuclear movements have been studied in detail, relatively little is known about signals from surrounding cells and tissues controlling these movements. Here, we show that, in gastrulating zebrafish embryos, convergence movements of nuclei within the yolk syncytial layer (YSL) are guided by mesoderm and endoderm progenitors migrating along the surface of the yolk towards the dorsal side of the developing gastrula. Progenitor cells direct the convergence movements of internal yolk syncytial nuclei (iYSN) by modulating cortical flow within the YSL in which the iYSN are entrained. The effect of mesoderm and endoderm progenitors on the convergence movement of iYSN depends on the expression of E-cadherin, indicating that adhesive contact between the cells and the YSL is required for the mesendoderm-modulated YSL cortical flow mediating nuclear convergence. In summary, our data reveal a crucial function for cortical flow in the coordination of syncytial nuclear movements with surrounding cells and tissues during zebrafish gastrulation.

  8. Multiscale diffusion in the mitotic Drosophila melanogaster syncytial blastoderm.

    Science.gov (United States)

    Daniels, Brian R; Rikhy, Richa; Renz, Malte; Dobrowsky, Terrence M; Lippincott-Schwartz, Jennifer

    2012-05-29

    Despite the fundamental importance of diffusion for embryonic morphogen gradient formation in the early Drosophila melanogaster embryo, there remains controversy regarding both the extent and the rate of diffusion of well-characterized morphogens. Furthermore, the recent observation of diffusional "compartmentalization" has suggested that diffusion may in fact be nonideal and mediated by an as-yet-unidentified mechanism. Here, we characterize the effects of the geometry of the early syncytial Drosophila embryo on the effective diffusivity of cytoplasmic proteins. Our results demonstrate that the presence of transient mitotic membrane furrows results in a multiscale diffusion effect that has a significant impact on effective diffusion rates across the embryo. Using a combination of live-cell experiments and computational modeling, we characterize these effects and relate effective bulk diffusion rates to instantaneous diffusion coefficients throughout the syncytial blastoderm nuclear cycle phase of the early embryo. This multiscale effect may be related to the effect of interphase nuclei on effective diffusion, and thus we propose that an as-yet-unidentified role of syncytial membrane furrows is to temporally regulate bulk embryonic diffusion rates to balance the multiscale effect of interphase nuclei, which ultimately stabilizes the shapes of various morphogen gradients.

  9. Detection of respiratory viruses by real-time polymerase chain reaction in outpatients with acute respiratory infection

    Directory of Open Access Journals (Sweden)

    Ronaldo Bragança Martins Júnior

    2014-09-01

    Full Text Available Viruses are the major contributors to the morbidity and mortality of upper and lower acute respiratory infections (ARIs for all age groups. The aim of this study was to determine the frequencies for a large range of respiratory viruses using a sensitive molecular detection technique in specimens from outpatients of all ages with ARIs. Nasopharyngeal aspirates were obtained from 162 individuals between August 2007-August 2009. Twenty-three pathogenic respiratory agents, 18 respiratory viruses and five bacteria were investigated using multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR and indirect immunofluorescence assay (IIF. Through IIF, 33 (20.4% specimens with respiratory virus were recognised, with influenza virus representing over half of the positive samples. Through a multiplex real-time RT-PCR assay, 88 (54.3% positive samples were detected; the most prevalent respiratory viral pathogens were influenza, human rhinovirus and respiratory syncytial virus (RSV. Six cases of viral co-detection were observed, mainly involving RSV. The use of multiplex real-time RT-PCR increased the viral detection by 33.9% and revealed a larger number of respiratory viruses implicated in ARI cases, including the most recently described respiratory viruses [human bocavirus, human metapneumovirus, influenza A (H1N1 pdm09 virus, human coronavirus (HCoV NL63 and HCoV HKU1].

  10. 特应质对呼吸道合胞病毒毛细支气管炎患儿鼻咽吸出物IL-4和IL-12及干扰素-γ水平的影响%Effect of Atopy on the IL-4,IL-12 and IFN-γ Levels in NPS of Respiratory Syncytial Virus Bronchiolitis in Infancy

    Institute of Scientific and Technical Information of China (English)

    姚欢银; 王伟; 王小仙; 刘淑梅; 陈啸洪

    2011-01-01

    Objective To study the effect of Atopy on the changes of IL - 4, IL - 12 and IFN - γ levels in NPS of respiratory syncytial virus bronchiolitis in infancy. Methods 49 infants with Bronchiolitis admitted from November 2008 to February 2009 were involved, with 30 cases in RSV positive group, 19 cases in RSV negative group and 23 cases in control group. The RSV positive group was further divided into atopy positive group (18 cases ) and atopy negative group (12 cases ) according to clinical features. The levels of IL-4, IL-12 and IFN-γ in NPS of each group were detected by ELISA technique. Results The level of IL -4 was significantly higher in group of RSV Bronchiolitis at acute stage [ ( 7. 0 ±4. 2 ) ng/L ] than RSV - negative Bronchiolitis group [ ( 4. 9 ± 2. 1 ) ng/L ] and control group [ ( 3. 7 ± 2. 1 ) ng/L ]; However, the level of IFN-γ in the group of RSV Bronchiolitis at acute stage [ ( 135. 3 ± 80. 7 ) ng/L ] was significantly lower than the RSV - Bronchiolitis group [ ( 277. 9 ± 100. 8 ) ng/L ] and control group [ ( 252. 7 ± 80. 2 ) ng/L ] ( P < 0. 01 ); IL - 12 levels in NPS was significantly higher in RSV - negative Bronchiolitis group [ ( 1214. 5 ± 871. 3 ) ng/L ] than RSV positive Bronchiolitis group [ ( 475. 1 ± 254. 0 ) ng/L ] and the control group [ ( 522. 7 ± 166. 6 ) ng/L ] ( P < 0. 01 ). IL-4 level was significantly higher in atopy positive RSV Bronchiolitis infected infants' NPS [ ( 9. 6 ± 3. 1 ) ng/L ] than in atopy negative infants [ ( 3. 1 ± 1. 5 ) ng/L ] and the control group [ ( 3. 7 ± 1. 5 ) ng/L ] ( P <0. 01 ). While the IL - 12 level in atopy positive RSV Bronchiolitis [ ( 341. 7 ± 132. 9 ) ng/L ] was significantly lower ( P <0. 05 ) than the RSV negative Bronchiolitis group [ ( 675. 2 ± 264. 6 ) ng/L ]. IFN-γ level of atopy positive group [ ( 153. 9 ± 95. 9 ) ng/L ] showed no significantly difference ( P >0. 05 ) compared with that of atopy negative group [ ( 107. 4 ± 39. 3 ) ng/L ] ( P > 0. 05

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    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...

  12. Respiratory mechanics

    CERN Document Server

    Wilson, Theodore A

    2016-01-01

    This book thoroughly covers each subfield of respiratory mechanics: pulmonary mechanics, the respiratory pump, and flow. It presents the current understanding of the field and serves as a guide to the scientific literature from the golden age of respiratory mechanics, 1960 - 2010. Specific topics covered include the contributions of surface tension and tissue forces to lung recoil, the gravitational deformation of the lung, and the interdependence forces that act on pulmonary airways and blood vessels. The geometry and kinematics of the ribs is also covered in detail, as well as the respiratory action of the external and internal intercostal muscles, the mechanics of the diaphragm, and the quantitative compartmental models of the chest wall is also described. Additionally, flow in the airways is covered thoroughly, including the wave-speed and viscous expiratory flow-limiting mechanisms; convection, diffusion and the stationary front; and the distribution of ventilation. This is an ideal book for respiratory ...

  13. Establishment of RT-PCR Method to Detect Bovine Parainfluenza Virus 3%牛副流感病毒3型RT—PCR检测方法的建立

    Institute of Scientific and Technical Information of China (English)

    刘晓乐; 张敏敏; 陈颖钰; 胡长敏; 陈焕春; 郭爱珍

    2011-01-01

    With the primers based on the complete genome sequence of bovine parainfluenza virus 3(BPIV-3) in GenBank, a PCR method for bovine parainfluenza virus 3 detection was developed. The optimum condition for annealing temperature was 58.1℃, primer concentration was 1.0μmol/L. By using this method, the specific fragment of 425 bp was amplified from BPIV-3 template, but not from other common virus and bacteria, such as bovine respiratory syncytial virus, bovine viral diarrhoea virus, infectious bovine rhinotracheitis virus and swine fever virus, mycoplasma bovis strain HB0801, Escherichia coll., Pasteurella muhocida type A and Salmonella typhimurium. The sensitivity of this PCR method was 10-3 TCID50/0.1mL.%参照GenBank中公布的牛副流感病毒3型(Bovineparainfluenzavirus3,BPIV-3)全基因序列,针对BPIV-3特异性NP蛋白保守基因设计一对引物,建立了BPIV-3的RT—PCR诊断方法。其最佳扩增退火温度为58.1℃,引物浓度为1.0μmol/L。采用该方法扩增BPIV-3参考病毒.能扩增出425bp预期大小的特异性片段,而扩增牛病毒性腹泻/黏膜病病毒、牛传染性鼻气管炎病毒、牛合胞体病毒、猪瘟病毒以及牛支原体、大肠埃希氏菌、牛巴氏杆菌和沙门氏菌等常见病毒和细菌均呈阴性结果。对参考病毒进行梯度稀释检测,结果证明该法检测BPIV-3的灵敏度可达10^-3FCID50/0.1mL。

  14. Effect of domestic bovine pulmonary surfactant on the prevention of neonatal respiratory distress syndrome%国产牛肺表面活性物质在预防新生儿呼吸窘迫综合征作用的探讨

    Institute of Scientific and Technical Information of China (English)

    李郑艳

    2015-01-01

    Objective To study the application value of domestic bovine pulmonary surfactant on the prevention of neonatal respiratory distress syndrome. Methods Ninety-four cases of premature infants were randomly divided into obser-vation group and control group, with 47 cases in each group. The newborn in the observation group were given the domestic bovine pulmonary surfactant 6 h after birth, the control group were not given. The blood gas, oxygenation index, the inci-dence of respiratory distress syndrome,the mechanical ventilation rate and fatality were compared between the two groups. Results In the observation group,PaO2 at 12, 24 h were (80. 2 ± 11. 6), (88. 6 ± 9. 1)mm Hg respectively, which were significantly higher than that in the control group (P 0. 05), after then that in the observation group was significantly higher than that in the control group (P 0. 05). Conclusions The clinical effect of domestic bovine pulmonary surfactant on the prevention of neonatal respiratory distress syndrome is re-markable, at the same time it can improve the clinical symptoms, reduce the occurrence of respiratory distress rate and im-prove the survival rate of newborn infants.%目的:研究国产牛肺表面活性物质对预防新生儿呼吸窘迫综合征的应用价值。方法将禹州市妇幼保健院94例早产儿随机分为观察组与对照组,每组47例,观察组新生儿出生6 h 后给予国产牛肺表面活性物质,对照组未应用。比较两组血气、氧合指标、呼吸窘迫综合征发生率、机械通气量率及病死率。结果观察组12、24 h PaO2分别为(80.2±11.6)、(88.6±9.1) mm Hg(1 mm Hg =0.133 kPa),显著高于对照组(P 0.05),后观察组显著高于对照组(P 0.05)。结论国产牛肺表面活性物质预防新生儿呼吸窘迫综合征的临床效果显著,同时可改善患儿临床症状,降低呼吸窘迫发生率,提高新生早产儿的存活率。

  15. [Bovine viral diarrhea control in Russian Federation].

    Science.gov (United States)

    Guliukin, M I; Iurov, K P; Glotov, A G; Donchenko, N A

    2013-01-01

    Bovine viral diarrhea (BVD) is one of the greatest challenges for breeding and commercial livestock. It is characterized by lesions of the respiratory and gastrointestinal tract, abortion, infertility, immune deficiency, and persistence of the pathogen. In this work, a set of measures for the rehabilitation and prevention of BVD in cattle is described. It includes the data of the literature, guidance documents for the diagnosis and control of BVD adopted by OIE, EU countries, USA, as well as the results of this research.

  16. Associations between co-detected respiratory viruses in children with acute respiratory infections.

    Science.gov (United States)

    Kaida, Atsushi; Kubo, Hideyuki; Takakura, Koh-ichi; Sekiguchi, Jun-ichiro; Yamamoto, Seiji P; Kohdera, Urara; Togawa, Masao; Amo, Kiyoko; Shiomi, Masashi; Ohyama, Minori; Goto, Kaoru; Hase, Atsushi; Kageyama, Tsutomu; Iritani, Nobuhiro

    2014-01-01

    Viruses are the major etiological agents of acute respiratory infections (ARIs) in young children. Although respiratory virus co-detections are common, analysis of combinations of co-detected viruses has never been conducted in Japan. Nineteen respiratory viruses or subtypes were surveyed using multiplex real-time PCR on 1,044 pediatric (patient age virus positive (1,414 viruses were detected), and 388 of the virus-positive specimens (43.5%, 388/891) were positive for multiple viruses. The ratio of multiple/total respiratory virus-positive specimens was high in children aged 0-35 months. Statistical analyses revealed that human bocavirus 1 and human adenovirus were synchronously co-detected. On the other hand, co-detections of human parainfluenza virus type 1 (HPIV-1) with HPIV-3, HPIV-3 with human metapneumovirus (hMPV), hMPV with respiratory syncytial virus A (RSV A), hMPV with influenza virus A (H1N1) 2009 (FLUA (H1N1) 2009), RSV A with RSV B, and human rhinovirus and FLUA (H1N1) 2009 were exclusive. These results suggest that young children (viruses, and some combinations of viruses are synchronously or exclusively co-detected.

  17. Hospital admissions for lower respiratory tract infections among infants in the Canadian Arctic: a cohort study

    Science.gov (United States)

    Banerji, Anna; Panzov, Val; Young, Michael; Robinson, Joan; Lee, Bonita; Moraes, Theo; Mamdani, Muhammad; Giles, B. Louise; Jiang, Depeng; Bisson, Danny; Dennis, Marguerite; Morel, Johanne; Hall, Judith; Hui, Charles; Paes, Bosco; Mahony, James B.

    2016-01-01

    Background: It is unknown whether this burden of disease of lower respiratory tract infections is comparable across the Canadian Arctic. The objectives of this surveillance study were to compare the rates of hospital admission for lower respiratory tract infection and the severity of infection across Arctic Canada, and to describe the responsible viruses. Methods: We performed a prospective multicentre surveillance study of infants less than 1 year of age admitted in 2009 with lower respiratory tract infection to all hospitals (5 regional, 4 tertiary) in the Northwest Territories, Nunavut and Nunavik to assess for regional differences. Nasopharyngeal aspirates were processed by means of a polymerase chain reaction respiratory viral panel, testing for 20 respiratory viruses and influenza A (H1N1). The role of coinfection was assessed by means of regression analysis for length of stay (short: 14 d). Outcomes compared included rates of lower respiratory tract infection, respiratory syncytial virus infection, transfer to tertiary hospital and severe lower respiratory tract infection (respiratory failure, intubation and mechanical ventilation, and/or cardiopulmonary resuscitation). Results: There were 348 admissions for lower respiratory tract infection in the population of interest in 2009. Rates of admission per 1000 live births varied significantly, from 39 in the Northwest Territories to 456 in Nunavik (p < 0.001). The rates of tertiary admissions and severe lower respiratory tract infection per 1000 live births in the Northwest Territories were 5.6 and 1.4, respectively, compared to 55.9 and 17.1, respectively, in Nunavut and 52.0 and 20.0, respectively, in Nunavik (p ≤ 0.001). Respiratory syncytial virus was the most common virus identified (124 cases [41.6% of those tested]), and coinfection was detected in 51 cases (41.1%) of infection with this virus. Longer length of stay was associated with coinfection (odds ratio [OR] 2.64) and underlying risk factors (OR