Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis.
Our aim was to obtain knowledge of how meteorological conditions affect community epidemics of respiratory syncytial virus (RSV) infection. To this end we recorded year-round RSV activity in nine cities that differ markedly in geographic location and climate. We correlated local weather conditions with weekly or monthly RSV cases. We reviewed similar reports from other areas varying in climate. Weekly RSV activity was related to temperature in a bimodal fashion, with peaks of activity at temperatures above 24-30 degrees C and at 2-6 degrees C. RSV activity was also greatest at 45-65% relative humidity. RSV activity was inversely related to UVB radiance at three sites where this could be tested. At sites with persistently warm temperatures and high humidity, RSV activity was continuous throughout the year, peaking in summer and early autumn. In temperate climates, RSV activity was maximal during winter, correlating with lower temperatures. In areas where temperatures remained colder throughout the year, RSV activity again became nearly continuous. Community activity of RSV is substantial when both ambient temperatures and absolute humidity are very high, perhaps reflecting greater stability of RSV in aerosols. Transmission of RSV in cooler climates is inversely related to temperature possibly as a result of increased stability of the virus in secretions in the colder environment. UVB radiation may inactivate virus in the environment, or influence susceptibility to RSV by altering host resistance.
Numerous studies have described a strong association between respiratory syncytial virus (RSV) infection in infancy and the development of recurrent wheezing and airway hyperresponsiveness. We evaluated the effect of an anti-RSV neutralizing monoclonal antibody (palivizumab) on different aspects of RSV disease by using a murine model. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or an isotype-matched control antibody was administered once at 24 h before inoculation, 1 h after inoculation, or 48 h after inoculation. Regardless of the timing of administration, all mice treated with the neutralizing antibody showed significantly decreased RSV loads in bronchoalveolar lavage (BAL) and lung specimens compared with those of infected controls. Pulmonary histopathologic scores, airway obstruction measured by plethysmography, and airway hyperresponsiveness after methacholine challenge were significantly reduced in mice treated with the anti-RSV antibody 24 h before inoculation compared with those for untreated controls. Concentrations of interferon-gamma, interleukin-10, macrophage inflammatory protein 1␣, regulated on activation normal T-cell expressed and secreted (RANTES), and eotaxin in BAL fluids were also significantly reduced in mice treated with palivizumab 24 h before inoculation. This study demonstrates that reduced RSV replication was associated with significant modulation of inflammatory and clinical markers of acute disease severity and significant improvement of the long-term pulmonary abnormalities. Studies to determine whether strategies aimed at preventing or reducing RSV replication could decrease the long-term morbidity associated with RSV infection in children should be considered.Respiratory syncytial virus (RSV) is the leading viral pathogen associated with lower respiratory tract disease in infants and young children worldwide. In addition to acute morbidity, numerous studies have described a strong association between RSV infection in infancy and the development of recurrent wheezing and airway hyperresponsiveness (AHR) (34,45,50). More recently, RSV has also been demonstrated to be an important cause of severe respiratory illness among the elderly and immunocompromised individuals (11, 12). Accordingly, efforts have been focused on both prevention and treatment of this common infection.Despite almost half a century of active clinical research on humans, as well as with animal and in vitro models, to define the immunopathogenesis of the disease, no effective vaccine is available yet, and the relationship between RSV and AHR remains to be completely characterized. In the United States, RSV is responsible for more than 150,000 hospitalizations per year in the pediatric population (49), resulting in an estimated annual cost of $300 million to $500 million for children below the age of 5 years (51, 57). Moreover, the long-term morbidity associated with severe RSV infection results in health care burdens and costs disproportionately greater than the estimated hospitalization costs ...
Respiratory tract infections result in wheezing in a subset of patients. Mycoplasma pneumoniae is a common etiologic agent of acute respiratory infection in children and adults that has been associated with wheezing in 20-40% of individuals. The current study was undertaken to elucidate the host-dependent pulmonary and immunologic response to M. pneumoniae respiratory infection by studying mice with different immunogenetic backgrounds (BALB/c mice versus C57BL/6 mice). After M. pneumoniae infection, only BALB/c mice developed significant airway obstruction (AO) compared with controls. M. pneumoniae-infected BALB/c mice manifested significantly elevated airway hyperresponsiveness (AHR) compared with C57BL/6 mice 4 and 7 d after inoculation as well as BALB/c control mice. Compared with C57BL/6 mice, BALB/c mice developed worse pulmonary inflammation, including greater peribronchial infiltrates. Infected BALB/c mice had significantly higher concentrations of tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-1beta, IL-6, IL-12, KC (functional IL-8), and macrophage inflammatory protein 1alpha in the bronchoalveolar lavage fluid compared with infected C57BL/6 mice. No differences in IL-2, IL-4, IL-5, IL-10, and granulocyte/macrophage colony-stimulating factor concentrations were found. The mice in this study exhibited host-dependent infection-related AO and AHR associated with chemokine and T-helper type (Th)1 pulmonary host response and not Th2 response after M. pneumoniae infection.
RSV A infections were more frequent than RSV B, and displayed greater variability. GA5 infections were associated with enhanced disease severity and distinct host immune responses.
Treatment of RSV-infected high-risk children with intravenous palivizumab alone or in combination with ribavirin was well tolerated and associated with decreased mortality compared with previous reports.
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