Respiratory syncytial virus infection in adults.
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Respiratory syncytial virus (RSV) is now recognized as a significant problem in certain adult populations. These include the elderly, persons with cardiopulmonary diseases, and immunocompromised hosts. Epidemiological evidence indicates that the impact of RSV in older adults may be similar to that of nonpandemic influenza. In addition, RSV has been found to cause 2 to 5% of adult community-acquired pneumonias. Attack rates in nursing homes are approximately 5 to 10% per year, with significant rates of pneumonia (10 to 20%) and death (2 to 5%). Clinical features may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing, and low-grade fever. Bone marrow transplant patients prior to marrow engraftment are at highest risk for pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably due to low viral titers in nasal secretions, but early bronchoscopy is valuable in immunosuppressed patients. Treatment of RSV in the elderly is largely supportive, whereas early therapy with ribavirin and intravenous gamma globulin is associated with improved survival in immunocompromised persons. An effective RSV vaccine has not yet been developed, and thus prevention of RSV infection is limited to standard infection control practices such as hand washing and the use of gowns and gloves. (+info)
Effect of coexpression of interleukin-2 by recombinant respiratory syncytial virus on virus replication, immunogenicity, and production of other cytokines.
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We constructed rRSV/mIL-2, a recombinant respiratory syncytial virus (rRSV) containing the coding sequence of murine interleukin-2 (mIL-2) in a transcription cassette inserted into the G-F intergenic region. The recovered virus (rRSV/mIL-2) expressed high levels (up to 2.8 microg/ml) of mIL-2 in cell culture. Replication of rRSV/mIL-2 in vitro was reduced up to 13.6-fold from that of wild-type (wt) rRSV, an effect that was due to the presence of the foreign insert but was not specific to mIL-2. Replication of the rRSV/mIL-2 virus in the upper and lower respiratory tracts of BALB/c mice was reduced up to 6.3-fold, an effect that was specific to mIL-2. The antibody response, including the levels of RSV-specific serum immunoglobulin G1 (IgG1), IgG2a, IgA, and total IgG, and the level of protective efficacy against wt RSV challenge were not significantly different from those of wt rRSV. Analysis of total pulmonary cytokine mRNA isolated 1 and 4 days following infection with rRSV/mIL-2 revealed elevated levels of mRNA for IL-2, gamma interferon (IFN-gamma), IL-4, IL-5, IL-6, IL-10, IL-13, and IL-12 p40 compared to those for wt rRSV. Flow cytometry of total pulmonary mononuclear cells isolated 10 days following infection with rRSV/mIL-2 revealed increased levels of CD4(+) T lymphocytes expressing either IFN-gamma or IL-4 compared to those of wt rRSV. These elevations in cytokine mRNA or cytokine-expressing CD4(+) cells relative to those of wt rRSV-primed animals were not observed following challenge with wt RSV on day 28. Thus, the expression of mIL-2 by rRSV was associated with a modest attenuation of virus growth in vivo, induction of serum antibodies at levels comparable to that of wt rRSV, and transient increases in both the Th1 and Th2 CD4(+) lymphocytes and cytokine mRNAs compared to those of wt rRSV. (+info)
Type 4 phosphodiesterase inhibitors attenuate respiratory syncytial virus-induced airway hyper-responsiveness and lung eosinophilia.
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Viral respiratory infections are considered one of the triggers of exacerbations of asthma. In a model of virus-induced airway hyper-responsiveness (AHR), mice infected with human respiratory syncytial virus (RSV) were shown to develop AHR accompanied by lung eosinophilia. Inhibitors of cyclic nucleotide phosphodiesterase (PDE) have been shown to affect airway responsiveness and pulmonary allergic inflammation. In this study, we assessed the effects of type 4 PDE (PDE4) inhibitors on AHR following RSV infection and compared them with a PDE3 inhibitor. In mice infected by intranasal inoculation of RSV, treatment with the PDE4 inhibitor rolipram or Ro-20-1724 reduced both AHR and the eosinophil infiltration of the airways. In contrast, the PDE3 inhibitor, milrinone, did not influence airway responsiveness or eosinophilic inflammation. These results demonstrate that PDE4 inhibitors can modulate RSV-induced AHR and lung eosinophilia and indicate that they have a potential role in treating exacerbations of asthma triggered by viral infection. (+info)
Specific and nonspecific obstructive lung disease in childhood: causes of changes in the prevalence of asthma.
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Reversible airway obstruction in childhood includes two major groups of patients: those with recurrent wheezing following bronchiolitis in early childhood, and those with allergic asthma, which represents an increasingly large proportion of cases through the school years. Over the last 40 years of the 20th century, allergic asthma has increased in many countries and in relation to several different allergens. Although this increase has differed in magnitude in different countries and also in the social groups most affected, it has had several features in common. The increase generally started between 1960 and 1970, has been progressive since then, and has continued into the 1990s without a defined peak. Among children 5-18 years of age, the increase has predominantly been among allergic individuals. Theories about the causes of the increase in asthma have focused on two scenarios: a) that changes in houses combined with increased time spent indoors have increased exposure to relevant allergens, or b) that changes in diet, antibiotic use, immunizations, and the pattern of infections in childhood have led to a change in immune responsiveness such that a larger section of the population makes T(H)2, rather than T(H)1 responses including IgE antibodies to inhalant allergens. There are, however, problems with each of these theories and, in particular, none of the proposed changes can explain the progressive nature of the increase over 40 years. The fact that the change in asthma has much in common with epidemic increase in diseases such as Type II diabetes or obesity suggests that similar factors could be involved. Several lines of evidence are reviewed that suggest that the decline in physical activity of children, particularly those living in poverty in the United States, could have contributed to the rise in asthma. The hypothesis would be that the progressive loss of a lung-specific protective effect against wheezing has allowed allergic children to develop symptomatic asthma. What is clear is that current theories do not provide either an adequate explanation of the increase or a practical approach to reversing the current trend. (+info)
Nosocomial respiratory syncytial virus infections: the "Cold War" has not ended.
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Respiratory syncytial virus (RSV) is a major nosocomial hazard on pediatric wards during its annual outbreaks. It produces significant morbidity in young children and is most severe in those with underlying conditions, especially cardiopulmonary and immunosuppressive diseases. In older patients, RSV may exacerbate an underlying condition or pulmonary and cardiac manifestations. On transplant units, of RSV may be occult and is associated with high mortality rates. The manifestations of nosocomial RSV infections may be atypical, especially in neonates and immunosuppressed patients, resulting in delayed or missed diagnosis and adding appreciably to the costs of hospitalization. RSV is primarily spread by close contact with infectious secretions, either by large-particle aerosols or by fomites and subsequent self-inoculation, and medical staff are often instrumental in its transmission. Thus, integral to any infection control program is the education of personnel about the modes of transmission, the manifestations, and the importance of RSV nosocomial infections. Hand washing is probably the most important infection control procedure. The choice of barrier controls should be decided by individual institutions depending on the patients, the type of ward, and the benefit relative to cost. (+info)
Respiratory syncytial virus infection in high risk infants and the potential impact of prophylaxis in a United Kingdom cohort.
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BACKGROUND: Bronchiolitis caused by respiratory syncytial virus (RSV) is an important cause of morbidity in ex-premature infants. In a randomised placebo controlled trial monoclonal antibody prophylaxis showed a 55% reduction in relative risk of hospital admission for these high risk infants, against a background incidence of 10.6 admissions per 100 high risk infants. AIMS: To follow a cohort of high risk infants in order to assess hospitalisation rate from RSV and the potential impact of prophylaxis for these patients in a UK local health authority. METHODS: A cohort of high risk infants from a local health authority were followed over the 1998/99 and 1999/2000 RSV seasons. The high risk population was defined as infants who, at the beginning of the seasons studied, were: (1) under 6 months old and born prior to 36 weeks gestation with no domiciliary oxygen requirement; or (2) under 24 months of age and discharged home in supplemental oxygen. All admissions with bronchiolitis during the season were identified. RESULTS: A total of 370 high risk infants were identified for the 1998/99 season and 286 for the following year. Over the two years there were 68 admissions. Significantly more admissions occurred from group 2 infants. RSV was identified in 27 cases (four admissions per hundred high risk infants). Prophylaxis may have saved up to pound 195,134 in hospital costs over the two years, but would have cost pound 1.1 million in drug acquisition costs. CONCLUSIONS: Careful consideration of risk factors is needed when selecting infants for RSV prophylaxis. (+info)
G protein variation in respiratory syncytial virus group A does not correlate with clinical severity.
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Respiratory syncytial virus group A strain variations of 28 isolates from The Netherlands collected during three consecutive seasons were studied by analyzing G protein sequences. Several lineages circulated repeatedly and simultaneously during the respective seasons. No relationships were found between lineages on the one hand and clinical severity or age on the other. (+info)
Evolution of bovine respiratory syncytial virus.
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Until now, the analysis of the genetic diversity of bovine respiratory syncytial virus (BRSV) has been based on small numbers of field isolates. In this report, we determined the nucleotide and deduced amino acid sequences of regions of the nucleoprotein (N protein), fusion protein (F protein), and glycoprotein (G protein) of 54 European and North American isolates and compared them with the sequences of 33 isolates of BRSV obtained from the databases, together with those of 2 human respiratory syncytial viruses and 1 ovine respiratory syncytial virus. A clustering of BRSV sequences according to geographical origin was observed. We also set out to show that a continuous evolution of the sequences of the N, G, and F proteins of BRSV has been occurring in isolates since 1967 in countries where vaccination was widely used. The exertion of a strong positive selective pressure on the mucin-like region of the G protein and on particular sites of the N and F proteins is also demonstrated. Furthermore, mutations which are located in the conserved central hydrophobic part of the ectodomain of the G protein and which result in the loss of four Cys residues and in the suppression of two disulfide bridges and an alpha helix critical to the three-dimensional structure of the G protein have been detected in some recent French BRSV isolates. This conserved central region, which is immunodominant in BRSV G protein, thus has been modified in recent isolates. This work demonstrates that the evolution of BRSV should be taken into account in the rational development of future vaccines. (+info)