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      Novel aspects on the pathogenesis of Mycoplasma pneumoniae pneumonia and therapeutic implications

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          Abstract

          Mycoplasma pneumoniae (Mp) is a leading cause of community acquired pneumonia. Knowledge regarding Mp pneumonia obtained from animal models or human subjects has been discussed in many different reports. Accumulated expertise concerning this critical issue has been hard to apply clinically, and potential problems may remain undiscovered. Therefore, our multidisciplinary team extensively reviewed the literature regarding Mp pneumonia, and compared findings from animal models with those from human subjects. In human beings, the characteristic pathological features of Mp pneumonia have been reported as alveolar infiltration with neutrophils and lymphocytes and lymphocyte/plasma cell infiltrates in the peri-bronchovascular area. Herein, we demonstrated the novel aspects of Mp pneumonia that the severity of the Mp pneumonia seemed to depend on the host innate immunity to the Mp, which might be accelerated by antecedent Mp exposure (re-exposure or latent respiratory infection) through up-regulation of Toll-like receptor 2 expression on bronchial epithelial cells and alveolar macrophages. The macrolides therapy might be beneficial for the patients with macrolide-resistant Mp pneumonia via not bacteriological but immunomodulative effects. This exhaustive review focuses on pathogenesis and extends to some therapeutic implications such as clarithromycin, and discusses the various diverse aspects of Mp pneumonia. It is our hope that this might lead to new insights into this common respiratory disease.

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          Most cited references179

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          BTS guidelines for the management of community acquired pneumonia in adults: update 2009.

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            Mycoplasma pneumoniae and its role as a human pathogen.

            Mycoplasma pneumoniae is a unique bacterium that does not always receive the attention it merits considering the number of illnesses it causes and the degree of morbidity associated with it in both children and adults. Serious infections requiring hospitalization, while rare, occur in both adults and children and may involve multiple organ systems. The severity of disease appears to be related to the degree to which the host immune response reacts to the infection. Extrapulmonary complications involving all of the major organ systems can occur in association with M. pneumoniae infection as a result of direct invasion and/or autoimmune response. The extrapulmonary manifestations are sometimes of greater severity and clinical importance than the primary respiratory infection. Evidence for this organism's contributory role in chronic lung conditions such as asthma is accumulating. Effective management of M. pneumoniae infections can usually be achieved with macrolides, tetracyclines, or fluoroquinolones. As more is learned about the pathogenesis and immune response elicited by M. pneumoniae, improvement in methods for diagnosis and prevention of disease due to this organism may occur.
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              Incidence of community-acquired pneumonia requiring hospitalization. Results of a population-based active surveillance Study in Ohio. The Community-Based Pneumonia Incidence Study Group.

              Pneumonia is the leading cause of death due to infectious diseases in the United States; however, the incidence of most infections causing community-acquired pneumonia in adults is not well defined. We evaluated all adults, residing in 2 counties in Ohio, who were hospitalized in 1991 because of community-acquired pneumonia. Information about risk factors, symptoms, and outcome was collected through interview and medical chart review. Serum samples were collected from consenting individuals during the acute and convalescent phases, and specific etiologic diagnoses were assigned based on results of bacteriologic and immunologic tests. The incidence of community-acquired pneumonia requiring hospitalization in the study counties in 1991 was 266.8 per 100,000 population; the overall case-fatality rate was 8.8%. Pneumonia incidence was higher among blacks than whites (337.7/100,000 vs 253.9/ 100,000; P or = 65 years; P < .001). Extrapolation from study incidence data showed the projected annual number of cases of community-acquired pneumonia requiring hospitalization in the United States to be 485,000. These data provide previously unavailable estimates of the annual number of cases that are due to Legionella species (8000-18,000), Mycoplasma pneumoniae (18,700-108,000), and Chlamydia pneumoniae (5890-49,700). These data provide information about the importance of community-acquired pneumonia and the relative and overall impact of specific causes of pneumonia. The study provides a basis for choosing optimal empiric pneumonia therapy, and allows interventions for prevention of pneumonia to be targeted at groups at greatest risk for serious illness and death.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                11 August 2014
                2014
                : 5
                : 410
                Affiliations
                [1] 1Department of Respiratory Medicine, Kyorin University School of Medicine Mitaka, Japan
                [2] 2Department of Virology and Immunology, College of Veterinary Medicine, Nippon Veterinary and Animal Science University Mitaka, Japan
                [3] 3Gunma Prefectural Institute of Public Health and Environmental Sciences Maebashi, Japan
                [4] 4Bioscience Medical Research Center, Niigata University Medical and Dental Hospital Niigata, Japan
                [5] 5Infectious Disease Surveillance Center, National Institute of Infectious Diseases Tokyo, Japan
                Author notes

                Edited by: Evangelos Giamarellos-Bourboulis, University of Athens, Greece

                Reviewed by: George Dimopoulos, Attikon University Hospital, Greece; Garyfallia Poulakou, Athens University School of Medicine, Greece

                *Correspondence: Hajime Goto, Department of Respiratory Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan e-mail: h510@ 123456ks.kyorin-u.ac.jp

                This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology.

                Article
                10.3389/fmicb.2014.00410
                4127663
                25157244
                4e5742b5-724a-4117-a61f-42248b53ebcd
                Copyright © 2014 Saraya, Kurai, Nakagaki, Sasaki, Niwa, Tsukagoshi, Nunokawa, Ohkuma, Tsujimoto, Hirao, Wada, Ishii, Nakata, Kimura, Kozawa, Takizawa and Goto.

                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) or licensor 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
                : 29 May 2014
                : 20 July 2014
                Page count
                Figures: 12, Tables: 3, Equations: 0, References: 190, Pages: 18, Words: 14536
                Categories
                Public Health
                Review Article

                Microbiology & Virology
                mycoplasma pneumoniae pneumonia,animal models,epidemiology,pathology,pathogenesis

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