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      Streptococcus pneumoniae’s Virulence and Host Immunity: Aging, Diagnostics, and Prevention

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          Abstract

          Streptococcus pneumoniae is an infectious pathogen responsible for millions of deaths worldwide. Diseases caused by this bacterium are classified as pneumococcal diseases. This pathogen colonizes the nasopharynx of its host asymptomatically, but overtime can migrate to sterile tissues and organs and cause infections. Pneumonia is currently the most common pneumococcal disease. Pneumococcal pneumonia is a global health concern and vastly affects children under the age of five as well as the elderly and individuals with pre-existing health conditions. S. pneumoniae has a large selection of virulence factors that promote adherence, invasion of host tissues, and allows it to escape host immune defenses. A clear understanding of S. pneumoniae’s virulence factors, host immune responses, and examining the current techniques available for diagnosis, treatment, and disease prevention will allow for better regulation of the pathogen and its diseases. In terms of disease prevention, other considerations must include the effects of age on responses to vaccines and vaccine efficacy. Ongoing work aims to improve on current vaccination paradigms by including the use of serotype-independent vaccines, such as protein and whole cell vaccines. Extending our knowledge of the biology of, and associated host immune response to S. pneumoniae is paramount for our improvement of pneumococcal disease diagnosis, treatment, and improvement of patient outlook.

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          Most cited references272

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          Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection.

          Nod2 activates the NF-kappaB pathway following intracellular stimulation by bacterial products. Recently, mutations in Nod2 have been shown to be associated with Crohn's disease, suggesting a role for bacteria-host interactions in the etiology of this disorder. We show here that Nod2 is a general sensor of peptidoglycan through the recognition of muramyl dipeptide (MDP), the minimal bioactive peptidoglycan motif common to all bacteria. Moreover, the 3020insC frameshift mutation, the most frequent Nod2 variant associated with Crohn's disease patients, fully abrogates Nod2-dependent detection of peptidoglycan and MDP. Together, these results impact on the understanding of Crohn's disease development. Additionally, the characterization of Nod2 as the first pathogen-recognition molecule that detects MDP will help to unravel the well known biological activities of this immunomodulatory compound.
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            The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America

            Abstract Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed. Areas that warrant future investigations are also highlighted.
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              Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine.

              Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children. Laboratory-confirmed IPD cases were identified during 1998-2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998-1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations. Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P< .01 all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P< .01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P< .05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006-2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old. Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.
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                Author and article information

                Contributors
                URI : https://frontiersin.org/people/u/555982
                URI : https://frontiersin.org/people/u/239419
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                22 June 2018
                2018
                : 9
                : 1366
                Affiliations
                [1] 1Microbiology and Molecular Genetics, Michigan State University , East Lansing, MI, United States
                [2] 2Institute for Quantitative Health Science & Engineering, Michigan State University , East Lansing, MI, United States
                [3] 3Biochemistry and Molecular Biology, Michigan State University , East Lansing, MI, United States
                Author notes

                Edited by: Amy Rasley, United States Department of Energy (DOE), United States

                Reviewed by: Jessica Lynn Humann, Florida A&M University, United States; Muhammad Zubair Shabbir, University of Veterinary and Animal Sciences, Pakistan

                *Correspondence: George I. Mias, gmias@ 123456msu.edu

                Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.01366
                6023974
                29988379
                df14e942-06f9-4b48-b2f1-e7421d576a7b
                Copyright © 2018 Brooks and Mias.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 March 2018
                : 01 June 2018
                Page count
                Figures: 9, Tables: 2, Equations: 0, References: 362, Pages: 29, Words: 25930
                Funding
                Funded by: Michigan State University 10.13039/100007709
                Funded by: National Human Genome Research Institute 10.13039/100000051
                Award ID: R00 HG007065
                Categories
                Immunology
                Review

                Immunology
                pneumococcal,pathogenesis,respiratory,immunology,virulence
                Immunology
                pneumococcal, pathogenesis, respiratory, immunology, virulence

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