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      The immunological mechanisms that control pneumococcal carriage

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          Abstract

          Colonization of the human nasopharynx by pneumococcus is extremely common and is both the primary reservoir for transmission and a prerequisite for disease. Current vaccines targeting the polysaccharide capsule effectively prevent colonization, conferring herd protection within vaccinated communities. However, these vaccines cover only a subset of all circulating pneumococcal strains, and serotype replacement has been observed. Given the success of pneumococcal conjugate vaccine (PCV) in preventing colonization in unvaccinated adults within vaccinated communities, reducing nasopharyngeal colonization has become an outcome of interest for novel vaccines. Here, we discuss the immunological mechanisms that control nasopharyngeal colonization, with an emphasis on findings from human studies. Increased understanding of these immunological mechanisms is required to identify correlates of protection against colonization that will facilitate the early testing and design of novel vaccines.

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          Most cited references68

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          Clinical and economic burden of community-acquired pneumonia among adults in Europe.

          It is difficult to determine the impact of community-acquired pneumonia (CAP) in Europe, because precise data are scarce. Mortality attributable to CAP varies widely between European countries and with the site of patient management. This review analysed the clinical and economic burden, aetiology and resistance patterns of CAP in European adults. All primary articles reporting studies in Europe published from January 1990 to December 2007 addressing the clinical and economic burden of CAP in adults were included. A total of 2606 records were used to identify primary studies. CAP incidence varied by country, age and gender, and was higher in individuals aged ≥65 years and in men. Streptococcus pneumoniae was the most common agent isolated. Mortality varied from <1% to 48% and was associated with advanced age, co-morbid conditions and CAP severity. Antibiotic resistance was seen in all pathogens associated with CAP. There was an increase in antibiotic-resistant strains, but resistance was not related to mortality. CAP was associated with high rates of hospitalisation and length of hospital stay. The review showed that the clinical and economic burden of CAP in Europe is high. CAP has considerable long-term effects on quality of life, and long-term prognosis is worse in patients with pneumococcal pneumonia.
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            The co-pathogenesis of influenza viruses with bacteria in the lung.

            Concern that a highly pathogenic virus might cause the next influenza pandemic has spurred recent research into influenza and its complications. Bacterial superinfection in the lungs of people suffering from influenza is a key element that promotes severe disease and mortality. This co-pathogenesis is characterized by complex interactions between co-infecting pathogens and the host, leading to the disruption of physical barriers, dysregulation of immune responses and delays in a return to homeostasis. The net effect of this cascade can be the outgrowth of the pathogens, immune-mediated pathology and increased morbidity. In this Review, advances in our understanding of the underlying mechanisms are discussed, and the key questions that will drive the field forwards are articulated.
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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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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Pathog
                PLoS Pathog
                plos
                plospath
                PLoS Pathogens
                Public Library of Science (San Francisco, CA USA )
                1553-7366
                1553-7374
                21 December 2017
                December 2017
                : 13
                : 12
                : e1006665
                Affiliations
                [1 ] Department of Clinicial Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
                [2 ] Department of Microbiology, New York University School of Medicine, New York, New York, United States of America
                [3 ] Division of Infectious Diseases, Boston Children′s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
                University of Basel, SWITZERLAND
                Author notes

                I have read the journal′s policy and have the following conflicts: RM is a named inventor on filed patents related to vaccine technologies and is a scientific founder, consultant, and equity owner at Affinivax, a biotechnology company based in Cambridge, MA that is devoted to the development of vaccines for developing and developed countries. RM is also a paid consultant to Merck & Co. in the area of adult immunizations. JNW receives royalties for a pneumococcal vaccine from GlaxoSmithKline Co. JNW has a financial interest in Merck & Co., which produces a pneumococcal vaccine.

                Author information
                http://orcid.org/0000-0002-4835-1032
                http://orcid.org/0000-0001-7168-8090
                http://orcid.org/0000-0002-0594-0902
                Article
                PPATHOGENS-D-17-01449
                10.1371/journal.ppat.1006665
                5739485
                29267378
                adff6831-a84f-410f-865c-ea95df5c368b
                © 2017 Jochems et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Page count
                Figures: 1, Tables: 0, Pages: 14
                Funding
                DMF is supported by the Medical Research Council (grant MR/M011569/1), Bill and Melinda Gates Foundation (grant OPP1117728), and the National Institute for Health Research (NIHR) Local Comprehensive Research Network. JNW is supported by NIH grants NIH/NIAID RO1 AI05168 and NIH/NIAID RO1 AI38446. RM is supported by grants from NIH, the Bill and Melinda Gates Foundation, and PATH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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