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      Severity of Pneumonia in Under 5-Year-Old Children from Developing Countries: A Multicenter, Prospective, Observational Study

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          Abstract.

          Pneumonia is the leading cause of death in children. The objectives were to evaluate the microbiological agents linked with hypoxemia in hospitalized children with pneumonia from developing countries, to identify predictors of hypoxemia, and to characterize factors associated with in-hospital mortality. A multicenter, observational study was conducted in five hospitals, from India (Lucknow, Vadu), Madagascar (Antananarivo), Mali (Bamako), and Paraguay (San Lorenzo). Children aged 2–60 months with radiologically confirmed pneumonia were enrolled prospectively. Respiratory and whole blood specimens were collected, identifying viruses and bacteria by real-time multiplex polymerase chain reaction (PCR). Microbiological agents linked with hypoxemia at admission (oxygen saturation < 90%) were analyzed by multivariate logistic regression, and factors associated with 14-day in-hospital mortality were assessed by bivariate Cox regression. Overall, 405 pneumonia cases (3,338 hospitalization days) were analyzed; 13 patients died within 14 days of hospitalization. Hypoxemia prevalence was 17.3%. Detection of human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in respiratory samples was independently associated with increased risk of hypoxemia (adjusted odds ratio [aOR] = 2.4, 95% confidence interval [95% CI] = 1.0–5.8 and aOR = 2.5, 95% CI = 1.1–5.3, respectively). Lower chest indrawing and cyanosis were predictive of hypoxemia (positive likelihood ratios = 2.3 and 2.4, respectively). Predictors of death were Streptococcus pneumoniae detection by blood PCR (crude hazard ratio [cHR] = 4.6, 95% CI = 1.5–14.0), procalcitonin ≥ 50 ng/mL (cHR = 22.4, 95% CI = 7.3–68.5) and hypoxemia (cHR = 4.8, 95% CI = 1.6–14.4). These findings were consistent on bivariate analysis. hMPV and RSV in respiratory samples were linked with hypoxemia, and S. pneumoniae in blood was associated with increased risk of death among hospitalized children with pneumonia in developing countries.

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          Most cited references23

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          Viral pneumonia.

          About 200 million cases of viral community-acquired pneumonia occur every year-100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies.

            Although radiological pneumonia is used as an outcome measure in epidemiological studies, there is considerable variability in the interpretation of chest radiographs. A standardized method for identifying radiological pneumonia would facilitate comparison of the results of vaccine trials and epidemiological studies of pneumonia. A WHO working group developed definitions for radiological pneumonia. Inter-observer variability in categorizing a set of 222 chest radiographic images was measured by comparing the readings made by 20 radiologists and clinicians with a reference reading. Intra-observer variability was measured by comparing the initial readings of a randomly chosen subset of 100 radiographs with repeat readings made 8-30 days later. Of the 222 images, 208 were considered interpretable. The reference reading categorized 43% of these images as showing alveolar consolidation or pleural effusion (primary end-point pneumonia); the proportion thus categorized by each of the 20 readers ranged from 8% to 61%. Using the reference reading as the gold standard, 14 of the 20 readers had sensitivity and specificity of > 0.70 in identifying primary end-point pneumonia; 13 out of 20 readers had a kappa index of > 0.6 compared with the reference reading. For the 92 radiographs deemed to be interpretable among the 100 images used for intra-observer variability, 19 out of 20 readers had a kappa index of > 0.6. Using standardized definitions and training, it is possible to achieve agreement in identifying radiological pneumonia, thus facilitating the comparison of results of epidemiological studies that use radiological pneumonia as an outcome.
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              Refining clinical diagnosis with likelihood ratios.

              Likelihood ratios can refine clinical diagnosis on the basis of signs and symptoms; however, they are underused for patients' care. A likelihood ratio is the percentage of ill people with a given test result divided by the percentage of well individuals with the same result. Ideally, abnormal test results should be much more typical in ill individuals than in those who are well (high likelihood ratio) and normal test results should be most frequent in well people than in sick people (low likelihood ratio). Likelihood ratios near unity have little effect on decision-making; by contrast, high or low ratios can greatly shift the clinician's estimate of the probability of disease. Likelihood ratios can be calculated not only for dichotomous (positive or negative) tests but also for tests with multiple levels of results, such as creatine kinase or ventilation-perfusion scans. When combined with an accurate clinical diagnosis, likelihood ratios from ancillary tests improve diagnostic accuracy in a synergistic manner.
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                Author and article information

                Journal
                Am J Trop Med Hyg
                Am. J. Trop. Med. Hyg
                tpmd
                The American Journal of Tropical Medicine and Hygiene
                The American Society of Tropical Medicine and Hygiene
                0002-9637
                1476-1645
                12 July 2017
                01 May 2017
                01 May 2017
                : 97
                : 1
                : 68-76
                Affiliations
                [1 ]Laboratoire des Pathogènes Emergents, Fondation Mérieux, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS, UMR5308, ENS de Lyon, UCBL1, Lyon, France
                [2 ]Service d'Hygiène, Epidémiologie et Prévention, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
                [3 ]Chhatrapati Shahu Ji Maharaj University, Lucknow, India;
                [4 ]KEM Hospital Research Centre, Pune, India
                [5 ]Hôpital Femme-Mère-Enfant, Antananarivo, Madagascar
                [6 ]Fondation Mérieux, Centre d'Infectiologie Charles Mérieux (CICM), Antananarivo, Madagascar
                [7 ]Gabriel Touré Hospital, Bamako, Mali
                [8 ]Centre d'Infectiologie Charles Mérieux (CICM), Bamako, Mali
                [9 ]Health Research Institute, Asuncion, Paraguay
                [10 ]Hospital Pediátrico “Niños de Acosta Ñu,” San Lorenzo, Paraguay
                [11 ]Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands
                Author notes
                [* ]Address correspondence to Gláucia Paranhos-Baccalà, Center of Excellence for Tropical Infectious Diseases, Medical Diagnostic Discovery Department (MD3), bioMérieux Brasil Av. Dr. Cardoso de Melo, 900 – Cj 42, 04548-003, São Paulo – SP, Brazil. E-mail: glaucia.baccala@ 123456biomerieux.com

                Financial support: This study was funded by Fondation Mérieux and the GABRIEL Network.

                Authors' addresses: Thomas Bénet and Philippe Vanhems, Laboratoire des Pathogènes Emergents, Fondation Mérieux, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France, and Service d'Hygiène, Epidémiologie et Prévention, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France, E-mails: thomas.benet@ 123456chu-lyon.fr and philippe.vanhems@ 123456chu-lyon.fr . Valentina Sanchez Picot, Florence Komurian-Pradel, Hubert Endtz, and Gláucia Paranhos-Baccalà, Laboratoire des Pathogènes Emergents, Fondation Mérieux, CIRI, INSERM U1111, CNRS UMR5308, ENS de Lyon, UCBL1, Lyon, France, E-mails: valentina.picot@ 123456fondation-merieux.org , florence.pradel@ 123456fondation-merieux.org , hubert.endtz@ 123456fondation-merieux.org , and glaucia.baccala@ 123456biomerieux.com . Shally Awasthi and Nitin Pandey, Chhatrapati Shahu Ji Maharaj University, Lucknow, India, E-mails: shally07@ 123456gmail.com and drnitinpandey@ 123456gmail.com . Ashish Bavdekar and Anand Kawade, KEM Hospital Research Centre, Pune, India, E-mails: bavdekar@ 123456vsnl.com and askawade@ 123456yahoo.com . Annick Robinson, Hôpital Femme-Mère-Enfant, Antananarivo, Madagascar, E-mail: annicklalaina@ 123456yahoo.fr . Mala Rakoto-Andrianarivelo, Fondation Mérieux, Centre d'Infectiologie Charles Mérieux (CICM), Antananarivo, Madagascar, E-mail: mala@ 123456cicm-madagascar.com . Maryam Sylla, Gabriel Touré Hospital, Bamako, Mali, E-mail: dr_mame@ 123456yahoo.fr . Souleymane Diallo, Centre d'Infectiologie Charles Mérieux (CICM), Bamako, Mali, E-mail: souleymane.diallo@ 123456fondationmerieux-mali.org . Graciela Russomando, Health Research Institute, Asuncion, Paraguay, E-mail: grusso@ 123456rieder.net.py . Wilma Basualdo, Hospital Pediátrico “Niños de Acosta Ñu,” San Lorenzo, Paraguay, E-mail: wilmabasualdo@ 123456gmail.com .

                Article
                tpmd160733
                10.4269/ajtmh.16-0733
                5508893
                28719310
                5e841a9d-ae0e-400e-935b-c4f3d614d64d
                © The American Society of Tropical Medicine and Hygiene

                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
                : 09 September 2016
                : 30 January 2017
                Page count
                Pages: 9
                Categories
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                Infectious disease & Microbiology
                Infectious disease & Microbiology

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