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ABSTRACT: Streptococcus pneumoniae is the leading cause of otitis media, sinusitis, and pneumonia. Many of these infections result from antecedent influenza virus infections. In this study we sought to determine whether the frequency and character of secondary pneumococcal infections differed depending on the strain of influenza virus that preceded bacterial challenge. In young ferrets infected with influenza virus and then challenged with pneumococcus, influenza viruses of any subtype increased bacterial colonization of the nasopharynx. Nine out of 10 ferrets infected with H3N2 subtype influenza A viruses developed either sinusitis or otitis media, while only 1 out of 11 ferrets infected with either an H1N1 influenza A virus or an influenza B virus did so. These data may partially explain why bacterial complication rates are higher during seasons when H3N2 viruses predominate. This animal model will be useful for further study of the mechanisms that underlie viral-bacterial synergism.
Infection and Immunity 06/2006; 74(5):2562-7. · 4.16 Impact Factor
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ABSTRACT: Secondary bacterial pneumonia is a common cause of death during influenza epidemics. We hypothesized that virus-specific factors could contribute to differences in annual excess mortality. Recombinant influenza viruses with neuraminidases from representative strains from the past 50 years were created and characterized. The specific level of their neuraminidase activity correlated with their ability to support secondary bacterial pneumonia. Recombinant viruses with neuraminidases from 1957 and 1997 influenza strains had the highest level of activity, whereas a virus with the neuraminidase from a 1968 strain had the lowest level of activity. The high level of activity of the neuraminidase from the 1957 strain, compared with that of other neuraminidases, more strongly supported the adherence of Streptococcus pneumoniae and the development of secondary bacterial pneumonia in a mouse model. These data lend support to our hypothesis that the influenza virus neuraminidase contributes to secondary bacterial pneumonia and subsequent excess mortality.
The Journal of Infectious Diseases 08/2005; 192(2):249-57. · 6.41 Impact Factor
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ABSTRACT: Viral-bacterial coinfections in humans are well-documented. Viral infections often lead to bacterial superinfections. In vitro and animal models for influenza, as well as molecular microbiology study of viruses and bacteria, provide an understanding of the mechanisms that explain how respiratory viruses and bacteria combine to cause disease. This article focuses on viral and bacterial combinations, particularly synergism between influenza and Streptococcus pneumoniae.
Potential mechanisms for synergism between viruses and bacteria include: virus destruction of respiratory epithelium may increase bacterial adhesion; virus-induced immunosuppression may cause bacterial superinfections; and inflammatory response to viral infection may up-regulate expression of molecules that bacteria utilize as receptors. Influenza and parainfluenza viruses possess neuraminidase (NA) activity, which appears to increase bacterial adherence after viral preincubation. Experimental studies demonstrate that viral NA exposes pneumococcal receptors on host cells by removing terminal sialic acids. Other studies show that inhibition of viral NA activity reduces adherence and invasion of S. pneumoniae, independently of effects on viral replication. Clinical studies reveal that influenza vaccination reduces the incidence of secondary bacterial respiratory tract infections.
Detection of viral factors (e.g. high NA activity) that increase the likely potential of epidemic/pandemic influenza strains for causing morbidity and mortality from secondary bacterial infections provides new possibilities for intervention. Additional study is needed to identify the mechanisms for the development of bacterial complications after infections with respiratory syncytial virus and other important respiratory viruses that lack NA activity. Prevention of bacterial superinfection is likely to depend on effective antiviral measures.
The Pediatric Infectious Disease Journal 02/2004; 23(1 Suppl):S87-97. · 3.58 Impact Factor
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ABSTRACT: Background: Mouse-adapted laboratory strains of influenza virus have to be used in mouse models of synergism between influenza virus and Streptococcus pneumoniae. Since ferrets support human influenza viruses without adaptation, we sought to characterize a ferret model of synergism between influenza and pneumococcus. Methods: Pairs of ferrets were infected with either influenza virus A/Sydney/5/97 or PBS then challenged 5 days later with either pneumococcus strain D39 or PBS. Clinical and laboratory parameters were monitored during a 48-h follow-up period after the challenge. Results: Ferrets receiving influenza then pneumococcus exhibited more severe clinical signs of illness and larger increases in WBC and segmental cell counts than did ferrets receiving influenza virus or pneumococcus alone. Pneumococcal nasal wash titers were higher in ferrets infected with influenza virus followed by pneumococcus than in those infected with pneumococcus alone. Histopathologic abnormalities in lungs were mild, but differences between sequentially infected and singly infected ferrets were observed. Conclusion: A sequential infection with influenza virus and pneumococcus causes a synergistic increase in morbidity in ferrets. This ferret model will be useful for study of the interactions between non-adapted human influenza viruses and S. pneumoniae.
International Congress Series 1263:486-490.
