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      Characterization of Cytomegalovirus Lung Infection in Non-HIV Infected Children

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          Abstract

          Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%), diffuse adventitious breath sounds (100%) and increased respiratory effort (93%). All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate) or histology/immunohistochemistry in lung biopsy (100% detection rate). CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes.

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          Most cited references25

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          Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments.

          After initial infection, human cytomegalovirus remains in a persistent state with the host. Immunity against the virus controls replication, although intermitent viral shedding can still take place in the seropositive immunocompetent person. Replication of cytomegalovirus in the absence of an effective immune response is central to the pathogenesis of disease. Therefore, complications are primarily seen in individuals whose immune system is immature, or is suppressed by drug treatment or coinfection with other pathogens. Although our increasing knowledge of the host-virus relationship has lead to the development of new pharmacological strategies for cytomegalovirus-associated infections, these strategies all have limitations-eg, drug toxicities, development of resistance, poor oral bioavailability, and low potency. Immune-based therapies to complement pharmacological strategies for the successful treatment of virus-associated complications should be prospectively investigated.
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            Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children. European Respiratory Society.

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              The immune response to human CMV.

              This review will summarize and interpret recent literature regarding the human CMV immune response, which is among the strongest measured and is the focus of attention for numerous research groups. CMV is a highly prevalent, globally occurring infection that rarely elicits disease in healthy immunocompetent hosts. The human immune system is unable to clear CMV infection and latency, but mounts a spirited immune-defense targeting multiple immune-evasion genes encoded by this dsDNA β-herpes virus. Additionally, the magnitude of cellular immune response devoted to CMV may cause premature immune senescence, and the high frequencies of cytolytic T cells may aggravate vascular pathologies. However, uncontrolled CMV viremia and life-threatening symptoms, which occur readily after immunosuppression and in the immature host, clearly indicate the essential role of immunity in maintaining asymptomatic co-existence with CMV. Approaches for harnessing the host immune response to CMV are needed to reduce the burden of CMV complications in immunocompromised individuals.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                07 May 2014
                May 2014
                : 6
                : 5
                : 2038-2051
                Affiliations
                [1 ]Division of Pediatric Pulmonology, Fundacion Hospital La Misericordia, Bogota 111411, Colombia; E-Mail: sm.restrepo@ 123456uniandes.edu.co
                [2 ]Department of Pediatrics, School of Medicine, Universidad de los Andes, Fundacion Santa Fe de Bogota, Bogota 110111, Colombia
                [3 ]Department of Pathology, School of Medicine, Universidad Nacional de Colombia, Bogota 111321, Colombia; E-Mail: millito59@ 123456hotmail.com
                [4 ]Department of Pathology, Fundación Hospital La Misericordia, Bogota 111411, Colombia
                [5 ]Department of Pediatrics, School of Medicine, Universidad Nacional de Colombia, Bogota 111321, Colombia; E-Mails: mikg376@ 123456gmail.com (M.G.-S.); carlos2671@ 123456gmail.com (C.E.R.-M.)
                [6 ]Department of Pediatric Pulmonology and Pediatric Critical Care Medicine, School of Medicine, Universidad El Bosque, Bogota 110111, Colombia
                [7 ]Research Unit, Military Hospital of Colombia, Bogota 111321, Colombia
                [8 ]Division of Pulmonary and Sleep Medicine, Children’s National Medical Center, Washington, DC 20010, USA; E-Mail: gperez@ 123456childrensnational.org
                [9 ]Division of Pediatric Rheumatology, Allergy and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; E-Mail: mgutierrez@ 123456hmc.psu.edu
                [10 ]Department of Integrative Systems Biology, Center for Genetic Medicine Research, Children’s National Medical Center, George Washington University, Washington, DC 20010, USA
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: gnino@ 123456childrensnational.org ; Tel.: +1-202-476-3194; Fax: +1-202-476-5864.
                Article
                viruses-06-02038
                10.3390/v6052038
                4036547
                24811320
                07349143-8650-4249-9437-5044da30a3b3
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 21 January 2014
                : 29 March 2014
                : 03 April 2014
                Categories
                Article

                Microbiology & Virology
                cmv,lung,pneumonia,children,ground glass
                Microbiology & Virology
                cmv, lung, pneumonia, children, ground glass

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