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      Streptococcus pneumoniae Otitis Media Pathogenesis and How It Informs Our Understanding of Vaccine Strategies

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          Abstract

          Purpose of Review

          This study aimed to review the literature regarding the mechanisms of transition from asymptomatic colonization to induction of otitis media and how the insight into the pathogenesis of otitis media has the potential to help design future otitis media-directed vaccines.

          Recent Findings

          Respiratory viruses have long been shown to predispose individuals to bacterial respiratory infections, such as otitis media. Recent information suggests that Streptococcus pneumoniae, which colonize the nasopharynx asymptomatically, can sense potentially “threatening” changes in the nasopharyngeal environment caused by virus infection by upregulating specific sets of genes involved in biofilm release, dissemination from the nasopharynx to other sites, and protection against the host immune system. Furthermore, an understanding of the transcriptional and proteomic changes occurring in bacteria during transition to infection has led to identification of novel vaccine targets that are disease-specific and will not affect asymptomatic colonization. This approach will avoid major changes in the delicate balance of microorganisms in the respiratory tract microbiome due to elimination of S. pneumoniae.

          Summary

          Our recent findings are reviewed in the context of the current literature on the epidemiology and pathogenesis of otitis media. We also discuss how other otopathogens, such as Haemophilus influenzae and Moraxella catarrhalis, as well as the normal respiratory microbiome, can modulate the ability of pneumococci to cause infection. Furthermore, the unsatisfactory protection offered by the pneumococcal conjugate vaccines is highlighted and we review potential future strategies emerging to confer a more specific protection against otitis media.

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          Most cited references81

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          Insights into the interaction between influenza virus and pneumococcus.

          Bacterial infections following influenza are an important cause of morbidity and mortality worldwide. Based on the historical importance of pneumonia as a cause of death during pandemic influenza, the increasingly likely possibility that highly pathogenic avian influenza viruses will trigger the next worldwide pandemic underscores the need to understand the multiple mechanisms underlying the interaction between influenza virus and bacterial pathogens such as Streptococcus pneumoniae. There is ample evidence to support the historical view that influenza virus alters the lungs in a way that predisposes to adherence, invasion, and induction of disease by pneumococcus. Access to receptors is a key factor and may be facilitated by the virus through epithelial damage, by exposure or up-regulation of receptors, or by provoking the epithelial regeneration response to cytotoxic damage. More recent data indicate that alteration of the immune response by diminishing the ability of the host to clear pneumococcus or by amplification of the inflammatory cascade is another key factor. Identification and exploration of the underlying mechanisms responsible for this synergism will provide targets for prevention and treatment using drugs and vaccines.
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            Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group.

            To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media. The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37,868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype. Other outcomes included overall impact on invasive disease regardless of serotype, effectiveness against clinical otitis media visits and episodes, impact against frequent and severe otitis media and ventilatory tube placement. In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears. In the interim analysis in August, 1998, 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100%. Blinded case ascertainment was continued until April, 1999. As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). There was no evidence of any increase of disease caused by nonvaccine serotypes. Efficacy for otitis media against visits, episodes, frequent otitis and ventilatory tube placement was 8.9, 7.0, 9.3 and 20.1% with P < 0.04 for all. In the analysis of spontaneously draining ears, serotype-specific effectiveness was 66.7%. This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media.
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              Pneumococcal conjugate vaccine for childhood immunization--WHO position paper.

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                Author and article information

                Contributors
                +46-725-19 02 55 , anders_p.hakansson@med.lu.se
                Journal
                Curr Otorhinolaryngol Rep
                Curr Otorhinolaryngol Rep
                Current Otorhinolaryngology Reports
                Springer US (New York )
                2167-583X
                20 May 2017
                20 May 2017
                2017
                : 5
                : 2
                : 115-124
                Affiliations
                ISNI 0000 0001 0930 2361, GRID grid.4514.4, Division of Experimental Infection Medicine, Department of Translational Medicine, Wallenberg Laboratory, , Lund University, ; Inga Marie Nilsson’s Street 53, 20502 Malmö, SE Sweden
                Article
                152
                10.1007/s40136-017-0152-6
                5446555
                28616365
                8c5d929c-5f05-41c0-9b12-38237d52a218
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Funded by: FundRef http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Funded by: FundRef http://dx.doi.org/10.13039/501100006310, Medicinska Forskningsrådet;
                Funded by: Österlunds Foundation
                Funded by: The Royal Physiographic Society
                Categories
                Pediatrics: Otitis Media in Children (A Hermansson, Section Editor)
                Custom metadata
                © Springer Science+Business Media New York 2017

                otitis media,streptococcus pneumonia,biofilm,microbiome,vaccine

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