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      Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines

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          Abstract

          Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization.

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          Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA.

          Maria da Glória S. Carvalho, Maria Tondella, Karen McCaustland … (2007)
          The accurate diagnosis of pneumococcal disease has frequently been hampered not only by the difficulties in obtaining isolates of the organism from patient specimens but also by the misidentification of pneumococcus-like viridans group streptococci (P-LVS) as Streptococcus pneumoniae. This is especially critical when the specimen comes from the respiratory tract. In this study, three novel real-time PCR assays designed for the detection of specific sequence regions of the lytA, ply, and psaA genes were developed (lytA-CDC, ply-CDC, and psaA, respectively). These assays showed high sensitivity (<10 copies for lytA-CDC and ply-CDC and an approximately twofold less sensitivity for psaA). Two additional real-time PCR assays for lytA and ply described previously for pneumococcal DNA detection were also evaluated. A panel of isolates consisting of 67 S. pneumoniae isolates (44 different serotypes and 3 nonencapsulated S. pneumoniae isolates from conjunctivitis outbreaks) and 104 nonpneumococcal isolates was used. The 67 S. pneumoniae isolates were reactive in all five assays. The new real-time detection assays targeting the lytA and psaA genes were the most specific for the detection of isolates confirmed to be S. pneumoniae, with lytA-CDC showing the greatest specificity. Both ply PCRs were positive for all isolates of S. pseudopneumoniae, along with 13 other isolates of other P-LVS isolates confirmed to be non-S. pneumoniae by DNA-DNA reassociation. Thus, the use of the ply gene for the detection of pneumococci can lead to false-positive reactions in the presence of P-LVS. The five assays were applied to 15 culture-positive cerebrospinal fluid specimens with 100% sensitivity; and serum and ear fluid specimens were also evaluated. Both the lytA-CDC and psaA assays, particularly the lytA-CDC assay, have improved specificities compared with those of currently available assays and should therefore be considered the assays of choice for the detection of pneumococcal DNA, particularly when upper respiratory P-LVS might be present in the clinical specimen.
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            Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children.

            Ian Michelow, Kurt Olsen, Juanita Lozano … (2004)
            The precise epidemiology of childhood pneumonia remains poorly defined. Accurate and prompt etiologic diagnosis is limited by inadequate clinical, radiologic, and laboratory diagnostic methods. The objective of this study was to determine as precisely as possible the epidemiology and morbidity of community-acquired pneumonia in hospitalized children. Consecutive immunocompetent children hospitalized with radiographically confirmed lower respiratory infections (LRIs) were evaluated prospectively from January 1999 through March 2000. Positive blood or pleural fluid cultures or pneumolysin-based polymerase chain reaction assays, viral direct fluorescent antibody tests, or viral, mycoplasmal, or chlamydial serologic tests were considered indicative of infection by those organisms. Methods for diagnosis of pneumococcal pneumonia among study subjects were published by us previously. Selected clinical characteristics, indices of inflammation (white blood cell and differential counts and procalcitonin values), and clinical outcome measures (time to defervescence and duration of oxygen supplementation and hospitalization) were compared among groups of children. One hundred fifty-four hospitalized children with LRIs were enrolled. Median age was 33 months (range: 2 months to 17 years). A pathogen was identified in 79% of children. Typical respiratory bacteria were identified in 60% (of which 73% were Streptococcus pneumoniae), viruses in 45%, Mycoplasma pneumoniae in 14%, Chlamydia pneumoniae in 9%, and mixed bacterial/viral infections in 23%. Preschool-aged children had as many episodes of atypical bacterial LRIs as older children. Children with typical bacterial or mixed bacterial/viral infections had the greatest inflammation and disease severity. Multivariate logistic-regression analyses revealed that high temperature (> or = 38.4 degrees C) within 72 hours after admission (odds ratio: 2.2; 95% confidence interval: 1.4-3.5) and the presence of pleural effusion (odds ratio: 6.6; 95% confidence interval: 2.1-21.2) were significantly associated with bacterial pneumonia. This study used an expanded diagnostic armamentarium to define the broad spectrum of pathogens that cause pneumonia in hospitalized children. The data confirm the importance of S pneumoniae and the frequent occurrence of bacterial and viral coinfections in children with pneumonia. These findings will facilitate age-appropriate antibiotic selection and future evaluation of the clinical effectiveness of the pneumococcal conjugate vaccine as well as other candidate vaccines.
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              Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies.

              Steven Obaro, David Greenberg, Rosanna Lagos … (2005)
              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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                Author and article information

                Contributors
                Manon Cevey-Macherel: +41-21-3143778 , +41-21-3143477 , manon.cevey-macherel@chuv.ch
                Journal
                Journal ID (nlm-ta): Eur J Pediatr
                Journal ID (iso-abbrev): Eur. J. Pediatr
                Title: European Journal of Pediatrics
                Publisher: Springer-Verlag (Berlin/Heidelberg )
                ISSN (Print): 0340-6199
                ISSN (Electronic): 1432-1076
                Publication date (Electronic): 24 February 2009
                Publication date (Print): 2009
                Volume: 168
                Issue: 12
                Pages: 1429-1436
                Affiliations
                [1 ]GRID grid.8515.9, ISNI 0000000104234662, Child and Adolescent Department, , Lausanne University Hospital, ; Lausanne, Switzerland
                [2 ]GRID grid.150338.c, ISNI 0000000107219812, Child and Adolescent Department, , University Hospital of Geneva, ; Geneva, Switzerland
                [3 ]GRID grid.8591.5, ISNI 0000000123224988, Center for Vaccine and Neonatal Immunology, Departments of Pediatrics and Pathology-Immunology, , University of Geneva, ; Geneva, Switzerland
                [4 ]GRID grid.9851.5, ISNI 0000000121654204, Institute of Microbiology, , University of Lausanne, ; Lausanne, Switzerland
                [5 ]GRID grid.150338.c, ISNI 0000000107219812, Central Laboratory of Virology, Division of Infectious Diseases and Faculty of Medicine, , University Hospital of Geneva, ; Geneva, Switzerland
                [6 ]GRID grid.8515.9, ISNI 0000000104234662, Pediatric Department, , Lausanne University Hospital, ; Rue du Bugnon 51, 1011 Lausanne, Switzerland
                Article
                Publisher ID: 943
                DOI: 10.1007/s00431-009-0943-y
                PMC ID: 7087130
                PubMed ID: 19238436
                SO-VID: a29c042a-d53f-450b-a2a3-3132307af21e
                Copyright © © Springer-Verlag 2009
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 25 July 2008
                Date accepted : 4 February 2009
                Categories
                Subject: Original Paper
                Custom metadata
                issue-copyright-statement © Springer-Verlag 2009

                ScienceOpen disciplines: Pediatrics
                Keywords: community-acquired pneumonia,child,who guidelines,pneumococcal infection,antibiotic,immunization
                Data availability:
                ScienceOpen disciplines: Pediatrics
                Keywords: community-acquired pneumonia, child, who guidelines, pneumococcal infection, antibiotic, immunization

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