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

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          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.

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          Most cited references29

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          Respiratory syncytial virus and parainfluenza virus.

          C Hall (2001)
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            Bronchiolitis-associated hospitalizations among US children, 1980-1996.

            Respiratory syncytial virus (RSV) causes more lower respiratory tract infections, often manifested as bronchiolitis, among young children than any other pathogen. Few national estimates exist of the hospitalizations attributable to RSV, and recent advances in prophylaxis warrant an update of these estimates. To describe rates of bronchiolitis-associated hospitalizations and to estimate current hospitalizations associated with RSV infection. Descriptive analysis of US National Hospital Discharge Survey data from 1980 through 1996. Children younger than 5 years who were hospitalized in short-stay, non-federal hospitals for bronchiolitis. Bronchiolitis-associated hospitalization rates by age and year. During the 17-year study period, an estimated 1.65 million hospitalizations for bronchiolitis occurred among children younger than 5 years, accounting for 7.0 million inpatient days. Fifty-seven percent of these hospitalizations occurred among children younger than 6 months and 81 % among those younger than 1 year. Among children younger than 1 year, annual bronchiolitis hospitalization rates increased 2.4-fold, from 12.9 per 1000 in 1980 to 31.2 per 1000 in 1996. During 1988-1996, infant hospitalization rates for bronchiolitis increased significantly (P for trend <.001), while hospitalization rates for lower respiratory tract diseases excluding bronchiolitis did not vary significantly (P for trend = .20). The proportion of hospitalizations for lower respiratory tract illnesses among children younger than 1 year associated with bronchiolitis increased from 22.2% in 1980 to 47.4% in 1996; among total hospitalizations, this proportion increased from 5.4% to 16.4%. Averaging bronchiolitis hospitalizations during 1994-1996 and assuming that RSV was the etiologic agent in 50% to 80% of November through April hospitalizations, an estimated 51, 240 to 81, 985 annual bronchiolitis hospitalizations among children younger than 1 year were related to RSV infection. During 1980-1996, rates of hospitalization of infants with bronchiolitis increased substantially, as did the proportion of total and lower respiratory tract hospitalizations associated with bronchiolitis. Annual bronchiolitis hospitalizations associated with RSV infection among infants may be greater than previous estimates for RSV bronchiolitis and pneumonia hospitalizations combined.
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              Extrapulmonary manifestations of severe respiratory syncytial virus infection – a systematic review

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

                Journal
                Respir Res
                Respiratory Research
                BioMed Central
                1465-9921
                1465-993X
                2010
                15 September 2010
                : 11
                : 1
                : 125
                Affiliations
                [1 ]Department of Pediatrics, Division of Infectious Diseases, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
                [2 ]Department of Pathology, University of Texas Southwestern Medical Center and Children's Medical Center Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
                [3 ]Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
                [4 ]Medimmune Inc., One Medimmune way, Gaithersburg, MD 20878, USA
                [5 ]Department of Pediatrics, Division of Infectious Diseases and Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, The Ohio State University, 700 Children's Drive, Columbus, OH 43205, USA
                Article
                1465-9921-11-125
                10.1186/1465-9921-11-125
                2946301
                20843364
                e56834ef-a535-4d7f-a0c0-826acd1b416c
                Copyright ©2010 Torres et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 May 2010
                : 15 September 2010
                Categories
                Research

                Respiratory medicine
                Respiratory medicine

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