Infection by Streptococcus pneumoniae in children with or without radiologically confirmed pneumonia

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"apellidos" => "Nascimento-Carvalho" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:9 [ 0 => array:3 [ "entidad" => "Universidade Federal da Bahia (UFBA), Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universidade Federal da Bahia (UFBA), Faculdade de Medicina, Departamento de Pediatria, Salvador, BA, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Universidade Federal da Bahia (UFBA), Faculdade de Medicina, Departamento de Medicina Interna e Apoio Diagnóstico, Salvador, BA, Brazil" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Universidade Federal da Bahia (UFBA), Complexo Hospitalar Professor Edgard Santos (HUPES), Salvador, BA, Brazil" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Valneva Austria GmbH, Campus Vienna Biocenter 3, Vienna, Austria" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Universidade Federal da Bahia (UFBA), Faculdade de Medicina, Departamento de Patologia, Salvador, BA, Brazil" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BA, Brazil" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Turku University and University Hospital, Department of Pediatrics, Turku, Finland" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "National Institute for Health and Welfare, Helsinki, Finland" "etiqueta" => "i" "identificador" => "aff0045" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Infecção por Streptococcus pneumoniae em crianças com ou sem pneumonia radiologicamente confirmada" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2426 "Ancho" => 2427 "Tamanyo" => 307564 ] ] "descripcion" => array:1 [ "en" => "Flow-chart showing inclusion/exclusion criteria for children included in this study." ] ] ] "textoCompleto" => "IntroductionCommunity acquired-pneumonia (CAP) is an important cause of morbidity and mortality in childhood.<a class="elsevierStyleCrossRef" href="#bib0155">1</a> However, the etiologic diagnosis of CAP is challenging. Chest radiographs have been used as a diagnostic tool by the identification of radiologic patterns suggestive of an inflammatory process, such as pulmonary infiltrates. Nevertheless, the role of chest radiograph in pediatric CAP remains controversial, due to problems observed in the routine use of this exam, such as poor inter-observer concordance<a class="elsevierStyleCrossRef" href="#bib0160">2</a> and the inability to distinguish between distinct etiologic agents.<a class="elsevierStyleCrossRefs" href="#bib0165">3,4</a> In turn, a significant proportion of children with a clinical diagnosis of CAP present normal chest radiograph upon admission,<a class="elsevierStyleCrossRef" href="#bib0175">5</a> and important differences in admission and evolution have been reported among children with CAP with or without radiological confirmation.<a class="elsevierStyleCrossRefs" href="#bib0180">6–9</a> Altogether, these data suggest that the disease in children with or without radiologically confirmed pneumonia might be caused by distinct mechanisms and/or different etiologic agents.In Brazil, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis have been reported as important bacterial agents of pediatric pneumonia in hospitalized children.<a class="elsevierStyleCrossRef" href="#bib0200">10</a> Herein, the presence of infection by S. pneumoniae, H. influenzae, and M. catarrhalis was investigated in non-hospitalized Brazilian children aged 2–59 months with clinical diagnosis of pneumonia with or without radiological confirmation. In doing so, the authors aimed to evaluate the role of the chest radiograph to identify probable cases of CAP caused by typical bacteria.MethodsStudy design and participantsThis prospective cohort study was part of a clinical trial that evaluated the use of oral amoxicillin given thrice or twice daily to 2–59 months-old children diagnosed with CAP (PNEUMOPAC-Efficacy trial, ClinicalTrials.gov <a href="ctgov:NCT01200706">NCT01200706</a>).<a class="elsevierStyleCrossRef" href="#bib0205">11</a> In that trial, 820 children were enrolled in the Emergency Department of the Universidade Federal da Bahia, in Salvador, Northeast Brazil, from November 2006 to May 2011. All children had a chest radiograph (frontal and lateral views) taken on admission, and blood samples were collected both at admission and at the follow-up visit, two to four weeks later. Inclusion criteria comprised the report of respiratory complaints and detection of lower respiratory findings, along with the presence of pulmonary infiltrate/consolidation on the chest radiograph according to the interpretation of the pediatrician on duty. Legal guardians of the included patients signed an informed consent upon enrollment.All chest radiographs were independently read by two pediatric radiologists (CAA-N and SCA), who were blinded to the clinical data. An overall agreement of 78.7% by these two pediatric radiologists was previously demonstrated.<a class="elsevierStyleCrossRef" href="#bib0175">5</a> If there was no concordance on the final diagnosis of any exam, this chest radiograph was then evaluated by a third radiologist (RVB). The radiologic findings were registered according to the standardized interpretation for epidemiological studies previously published by the World Health Organization.<a class="elsevierStyleCrossRef" href="#bib0210">12</a> Radiologically confirmed pneumonia was defined as the presence of pulmonary infiltrate or consolidation in two independent assessments.The use of pneumococcal conjugate vaccine-10 (PCV10) was universally implemented in Salvador, Brazil, in July 2010, for children aged <2 years.<a class="elsevierStyleCrossRef" href="#bib0215">13</a> Every child included in the PNEUMOPAC-efficacy trial who could have received PCV10 had the vaccine card checked personally by one of the researchers (ICB) after the trial was completed. Patients who received any dose of PCV10 and those whose vaccine status could not be identified were excluded from this analysis. Patients with severe malnutrition, defined as Z-score for weight-for-age under −3.00,<a class="elsevierStyleCrossRef" href="#bib0220">14</a> were also excluded. Nutritional evaluation was performed using the Anthro software. Children with lower-chest in-drawing or danger signs (inability to drink, convulsions, central cyanosis, grunting in a calm child) were excluded from the PNEUMOPAC-efficacy trial, as well as those with underlying chronic diseases.This study was approved by the Ethics Committee of the Universidade Federal da Bahia and was conducted in accordance with the principles of the Declaration of Helsinki.Laboratory proceduresFluorescent multiplexed bead-based immunoassay was used to quantify the levels of antibodies against protein antigens from S. pneumoniae, H. influenzae and M. catarrhalis using Luminex xMAP® technology (Luminex Corporation, TX, USA).<a class="elsevierStyleCrossRef" href="#bib0225">15</a> This assay included eight recombinant proteins from S. pneumoniae (pneumolysin [Ply], choline binding protein A [CbpA], pneumococcal surface protein A families 1 and 2 [PspA1 and PspA2], pneumococcal choline binding protein A [PcpA], pneumococcal histidine triad protein D [PhtD], serine/threonine protein kinase [StkP-C, SP1732-3], and protein required for cell wall separation of group B streptococcus [PcsB-N, SP2216-1]), three recombinant proteins from H. influenzae (NTHi Protein D, NTHi0371-1, and NTHi0830), and five recombinant proteins from M. catarrhalis (MC Omp CD, MC_RH4_2506, MC_RH4_1701, MC_RH4_3729-1, and MC_RH4_4730). Nine bead sets were created using the aforementioned proteins in the following combination: Ply, CbpA, PcpA, PhtD, StkP-C, and PcsB-N were conjugated in one bead region each; PspA1 and PspA2 were conjugated in the same bead region; and all H. influenzae and all M. catarrhalis proteins were conjugated in one bead region per bacterium.This assay provided the mean fluorescence intensity (MFI) values for each antigen and serum evaluated. The MFI value represents an indirect measure of the IgG concentration against the studied antigens. True duplicates were used throughout the procedure and their fluorescence readings were averaged. To ensure the repeatability of the assays, high and low controls were analyzed on each plate. Furthermore, acute and convalescent samples were always analyzed on the same plate. All samples were tested using 1:400 and 1:1600 dilutions and, if necessary, further dilutions were performed. The occurrence of a serological response against S. pneumoniae was defined as an increase in the antibody levels ≥2-fold for IgG against Ply, CbpA, PspA1 and PspA2, PhtD, StkP-C, and PcsB-N, or an increase ≥1.5-fold for IgG against PcpA, based on the validation of a sensitive and specific serological test for the diagnosis of invasive pneumococcal disease.<a class="elsevierStyleCrossRef" href="#bib0230">16</a> The diagnosis of infection by S. pneumoniae was established by the detection of serological response against any of the evaluated antigens, based on the specificity of the assay and good correlation with ELISA.<a class="elsevierStyleCrossRef" href="#bib0225">15</a> The sensitivity and specificity for a serological response against each antigen were previously published.<a class="elsevierStyleCrossRef" href="#bib0230">16</a> The occurrence of infection by H. Influenzae or M. catarrhalis was defined as an increase in antibody levels ≥2-fold between acute and convalescent samples.<a class="elsevierStyleCrossRefs" href="#bib0225">15,17</a> All serological tests were performed by DCA and ICB at the National Institute for Health and Welfare, in Helsinki, Finland. The frequency of these infections analyzed by age distribution, interval of sample collection, and duration of disease has been published elsewhere.<a class="elsevierStyleCrossRef" href="#bib0235">17</a>Statistical analysisCategorical variables were compared using the chi-squared or Fisher's exact tests as appropriate, and continuous variables were evaluated using Mann–Whitney's U test, as they presented non-parametric distribution. The negative predictive value of the normal chest radiograph for the diagnosis of infection by S. pneumoniae was calculated. Multivariate logistic regression was performed using the presence of radiologically confirmed pneumonia as the dependent variable and infection by S. pneumoniae as the independent variable. This model was adjusted by age and infection by H. influenzae or M. catarrhalis. All statistical tests were two-tailed, with a significance level of 0.05. The software Stata/SE 12.0 (StataCorp. 2011. Stata Statistical Software: Release 12. College Station, TX, USA) was used to calculate the negative predictive value of the normal chest radiograph, and the software SPSS (SPSS Inc., version 9.0. Chicago, USA) was used for the remaining analyzes.ResultsOut of 820 patients included in the PNEUMOPAC-efficacy trial, 615 were included in this study, of whom 249 (40.5%) had radiologically confirmed pneumonia and 366 (59.5%) had normal chest radiograph. <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the flowchart of the included and excluded cases in this investigation. Overall, 311 (50.6%) were males and the median age was 27.2 months (25th–75th percentile: 14.9–41.4 months). Consolidation was detected by radiologists 1, 2, and 3 in 84.6%, 79.8%, and 67.3% of the cases with concordant radiologically confirmed pneumonia, respectively. The remaining cases of radiologically confirmed pneumonia were diagnosed based on the detection of pulmonary infiltrates.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The comparison of the levels of antibodies on admission (first serum sample) against the studied antigens using a 1:1600 dilution factor is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Children with radiologically confirmed pneumonia had significantly higher levels of antibodies against several protein antigens from S. pneumoniae and H. influenzae, and lower levels of antibodies against M. catarrhalis proteins. Similar results were obtained when using a 1:400 dilution factor (data not shown). Children with radiologically confirmed pneumonia also presented a higher frequency of infection by S. pneumoniae. Antibody responses against S. pneumoniae proteins were detected in 28.5% of the children with radiologically confirmed pneumonia and in 13.7% of children with a normal chest radiograph (p<0.001). Antibody responses against PcpA, PhtD, and PcsB were most frequently detected in children with radiologically confirmed pneumonia. These results are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. When the levels of antibodies against the studied antigens on the second serum sample were compared using a 1:1600 dilution factor, higher levels of IgG against all proteins from S. pneumoniae and H. influenzae were observed, as well as lower levels of antibodies against M. catarrhalis, as shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. Similar results were obtained when using a 1:400 dilution factor (data not shown).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>A multivariate logistic regression was performed to assess the effect of infection by S. pneumoniae on the presence of radiologically confirmed pneumonia, adjusting this model by infection by H. influenzae or M. catarrhalis and age. The presence of infection by S. pneumoniae increased the odds of radiologically confirmed pneumonia by 2.8 (95% CI: 1.8–4.3). The presence of infection by either H. influenzae or M. catarrhalis or the age of the child did not affect the odds for detection of radiologically confirmed pneumonia (odds radio [95% CI]: 1.42 [0.7–2.9]; 0.4 [0.1–1.6]; and 0.9 [0.9–1], respectively). Furthermore, the negative predictive value of the normal chest radiograph for the diagnosis of infection by the pneumococcus was 86.3% (95% CI: 82.4–89.7%).DiscussionThis study demonstrated that children with radiologically confirmed pneumonia have a higher frequency of infection by S. pneumoniae than those with a normal chest radiograph. The presence of infection by pneumococcus was independently associated to radiologically confirmed pneumonia among non-hospitalized children with clinical CAP. Furthermore, the presence of a normal chest radiograph had a high negative predictive value for the detection of antibody responses against S. pneumoniae.A higher frequency of antibody response against several antigens from S. pneumoniae was observed in the group of children with radiologically confirmed pneumonia when compared with those with a normal chest radiograph. This finding corroborates the results from previous studies, which demonstrated that the presence of alveolar infiltrates on chest radiographs was associated with bacterial pneumonia.<a class="elsevierStyleCrossRef" href="#bib0240">18</a> For instance, Nascimento-Carvalho et al. also reported that infection by S. pneumoniae was more frequently detected among hospitalized children with CAP who presented radiographic pneumonia rather than those with a normal chest radiograph.<a class="elsevierStyleCrossRef" href="#bib0245">19</a> In turn, children with a normal chest radiograph had a higher incidence of viral infection.<a class="elsevierStyleCrossRef" href="#bib0245">19</a> This is the first report of the association between pneumococcal infection and radiologically confirmed pneumoniae among non-hospitalized children with clinical CAP.Accordingly, the negative predictive value of the normal chest radiograph for the detection of pneumococcal infection was high (86.3% [95% CI: 82.4–89.7%]). Although an association between bacterial infection and alveolar infiltrates/consolidation has been previously described,<a class="elsevierStyleCrossRef" href="#bib0240">18</a> these findings cannot reliably establish the etiologic diagnosis of CAP.<a class="elsevierStyleCrossRefs" href="#bib0170">4,5</a> Therefore, the present finding that the normal chest radiograph has a high negative predictive value for pneumococcal infection may aid in the interpretation of this exam. The high negative predictive value observed for the normal chest radiograph in a population with high prevalence of pneumococcal infection is noteworthy,<a class="elsevierStyleCrossRef" href="#bib0200">10</a> thereby reinforcing the present results. Altogether, the present data indicate that children with non-severe CAP with radiologically confirmed pneumonia have a higher chance of infection by S. pneumoniae, whereas children with a normal chest radiograph are not likely to present infection by this agent and might not benefit from empiric antibiotic therapy.Data from vaccine trials reinforce the relationship between pneumococcal infection and radiologically confirmed pneumonia, as a differential effect of pneumococcal vaccination was found on the rates of pediatric CAP depending on the applied diagnostic criteria. For instance, the efficacy of the PCV10 was significantly higher for children with consolidation on the chest radiograph than for children either with alveolar infiltrates or solely with a clinical diagnosis of CAP.<a class="elsevierStyleCrossRef" href="#bib0250">20</a> Therefore, the greater impact of pneumococcal vaccination on children with consolidation on chest radiographs suggests that patients with this radiological diagnosis present a higher incidence of pneumococcal infection. These findings are consistent with those reported by Lucero et al., who demonstrated a good vaccine efficacy of PCV11 on children with radiographic pneumonia defined as consolidation and a practicably negligible vaccine efficacy for children with a clinical diagnosis of pneumonia.<a class="elsevierStyleCrossRef" href="#bib0255">21</a> These vaccine trials provide indirect evidence regarding the etiology of pneumonia in children with distinct radiological patterns, indicating that children with radiologically confirmed pneumonia indeed present a higher frequency of infection by S. pneumoniae.The role of the chest radiograph in the management of children with CAP, however, has been largely debated. Importantly, Bradley et al. recommend that the chest radiograph should only be used in children who are hospitalized or with hypoxemia, significant respiratory distress, suspected complications, or therapy failure.<a class="elsevierStyleCrossRef" href="#bib0260">22</a> This position is corroborated by Harris et al., who stated that children with signs and symptoms suggesting pneumonia who are not admitted to hospital should not routinely have a chest radiograph.<a class="elsevierStyleCrossRef" href="#bib0265">23</a> These recommendations are partly due to previous studies that have shown that bacterial pneumonia cannot be differentiated from non-bacterial pneumonia based solely on the findings of an abnormal chest radiograph.<a class="elsevierStyleCrossRefs" href="#bib0165">3,4,24</a> Furthermore, the current evidence suggests that the use of a chest radiograph does not improve the outcome of pediatric patients with CAP.<a class="elsevierStyleCrossRef" href="#bib0275">25</a> Nonetheless, it is important to emphasize that when the impact of the chest radiograph on the management of children with CAP was evaluated, the patients received antibiotics at the discretion of the attending physician, regardless of the radiologic findings, thereby limiting the potential benefit of a radiological study in these patients as a diagnostic tool with therapeutic implications.<a class="elsevierStyleCrossRef" href="#bib0275">25</a> Accordingly, Harris et al. recommend the use of antibiotics for all children with a clear diagnosis of CAP.<a class="elsevierStyleCrossRef" href="#bib0265">23</a> Both guidelines agree, however, that young children do not require routine use of antibiotics, as most present viral acute lower respiratory infection.<a class="elsevierStyleCrossRefs" href="#bib0260">22,23</a> In this scenario, although the chest radiograph does not unequivocally distinguish etiologic agents of CAP, it may help differentiating distinct patterns of lower respiratory infections. Recent evidence has demonstrated important differences between children with or without radiologically confirmed pneumonia in the clinical presentation and evolution. Children with radiologically confirmed pneumonia have a higher frequency and longer persistence of fever,<a class="elsevierStyleCrossRefs" href="#bib0180">6–8</a> and also evolve more severely, with longer hospitalization, higher need of respiratory support, and higher rates of treatment failure.<a class="elsevierStyleCrossRef" href="#bib0195">9</a> These differences indicate that children with and without radiologically confirmed pneumonia may have different patterns of lower respiratory tract infection, and the chest radiograph, when performed, may aid the management of doubtful cases of non-severe CAP.It was also observed that children with radiologically confirmed pneumonia had higher levels of antibodies against several pneumococcal proteins both at admission and in convalescence. Lower levels of anti-pneumococcal antibodies on admission have been associated with a higher frequency of antibody responses against S. pneumoniae due to particularities of the serological methods.<a class="elsevierStyleCrossRef" href="#bib0235">17</a> Therefore, the level of antibodies at admission probably was not responsible for the higher rate of antibody responses against the pneumococcus in children with radiological pneumonia. The higher level of antibodies at admission in this group of children, in turn, might have been caused by previous colonization by S. pneumoniae. Nasopharyngeal colonization has been recognized as part of the natural history of pneumococcal disease, which ensues if immunological barriers are crossed by the colonizing bacteria.<a class="elsevierStyleCrossRef" href="#bib0280">26</a> Also, children with clinical and radiological pneumonia are also more frequently colonized with S. pneumoniae when compared with healthy controls.<a class="elsevierStyleCrossRef" href="#bib0285">27</a> Therefore, it is possible that a higher rate of carriage of S. pneumoniae in children with radiologically confirmed pneumonia elicited the higher levels of anti-pneumococcal antibodies found in this subgroup.No difference was observed on the rates of antibody response against H. influenzae and M. catarrhalis in this study, possibly due to the low numbers of responders within the study group. However, discretely higher levels of antibodies against H. influenzae were found in children with radiologically confirmed pneumonia, as well as lower levels of antibodies against M. catarrhalis. It is known that several bacterial agents compete to colonize the nasopharyngeal tract of pediatric patients, creating a dynamic process of turnover of colonizing agents.<a class="elsevierStyleCrossRef" href="#bib0285">27</a> Increased rates of colonization by S. pneumoniae might also have contributed to lower the levels of antibodies against M. catarrhalis on the samples collected from children with radiologically confirmed pneumonia at admission. In turn, a positive correlation between colonization by S. pneumoniae and H. influenzae has already been described, which may have contributed to the high levels of antibodies at admission found against H. influenzae.<a class="elsevierStyleCrossRef" href="#bib0290">28</a>The limitations of the present study must be emphasized. Firstly, data on the colonization status of the evaluated children were not available, and the putative effect of pneumococcal carriage on the antibody levels at admission was not evaluated. Secondly, the study was composed of unvaccinated children, which does not represent the reality in most countries in the post-PCV era. Nevertheless, recent evidence suggests that the use of PCV does not interfere with the result of protein-based serological assays in children with CAP,<a class="elsevierStyleCrossRef" href="#bib0295">29</a> which favors the generalization of the present results. Also, data on the use of other vaccines that could have influenced the results presented herein, such as the H. influenzae type b vaccine, was not available. However, the coverage of the H. influenzae type b vaccine among the pediatric population in Brazil is high (>80%), so differential rates of vaccination probably did not affect the present results.<a class="elsevierStyleCrossRef" href="#bib0300">30</a> Finally, as all antigens from H. influenzae and M. catarrhalis were conjugated in one bead region per bacterium, individual fluorescence readings were not obtained for these antigens.In conclusion, this study demonstrated that, among non-hospitalized children with clinical CAP who were submitted to a chest radiograph, those with radiologically confirmed pneumonia had a higher frequency of infection by S. pneumoniae compared to children with a normal chest radiograph. Furthermore, the presence of pneumococcal infection was independently associated with radiologically confirmed pneumonia; normal chest radiograph has a high negative predictive value for pneumococcal infection.FundingSanofi Pasteur (Lyon, France) supplied PcpA and PhtD; Prof. Elaine Tuomanen at St. Judes Children's Research Hospital (Memphis, United States) supplied Ply, CbpA, PspA1; Profs. Susan Hollingshead, David Briles, and Pat Coan at University of Alabama (Birmingham, United States) supplied PspA2; and Valneva Austria GmbH (Vienna, Austria) supplied StkP-C, PcsB-N, NTHi Protein D, NTHi0371-1, NTHi0830, MC Omp CD, MC_RH4_2506, MC_RH4_1701, MC_RH4_3729-1, and MC_RH4_4730.This work was supported by the Bahia State Agency for Research Funding (Fundação de Amparo à Pesquisa do Estado da Bahia [FAPESB]) and the Brazilian Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq]).Conflicts of interestAndreas Meinke is an employee of Valneva Austria GmbH. The others authors declare no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1402825" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1284271" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1402824" "titulo" => "Resumo" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1284272" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design and participants" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Laboratory procedures" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack487972" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-10-30" "fechaAceptado" => "2017-01-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1284271" "palabras" => array:5 [ 0 => "Bacterial infection" 1 => "Etiology" 2 => "Lower respiratory tract infection" 3 => "Radiological study" 4 => "Serological tests" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec1284272" "palabras" => array:5 [ 0 => "Infecção bacteriana" 1 => "Etiologia" 2 => "Infecção do trato respiratório inferior" 3 => "Estudo radiológico" 4 => "Testes sorológicos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveCommunity-acquired pneumonia is an important cause of morbidity in childhood, but the detection of its causative agent remains a diagnostic challenge. The authors aimed to evaluate the role of the chest radiograph to identify cases of community-aquired pneumonia caused by typical bacteria. MethodsThe frequency of infection by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis was compared in non-hospitalized children with clinical diagnosis of community acquired pneumonia aged 2–59 months with or without radiological confirmation (n=249 and 366, respectively). Infection by S. pneumoniae was diagnosed by the detection of a serological response against at least one of eight pneumococcal proteins (defined as an increase ≥2-fold in the IgG levels against Ply, CbpA, PspA1 and PspA2, PhtD, StkP-C, and PcsB-N, or an increase ≥1.5-fold against PcpA). Infection by H. influenzae and M. catarrhalis was defined as an increase ≥2-fold on the levels of microbe-specific IgG. ResultsChildren with radiologically confirmed pneumonia had higher rates of infection by S. pneumoniae. The presence of pneumococcal infection increased the odds of having radiologically confirmed pneumonia by 2.8 times (95% CI: 1.8–4.3). The negative predictive value of the normal chest radiograph for infection by S. pneumoniae was 86.3% (95% CI: 82.4–89.7%). There was no difference on the rates of infection by H. influenzae and M. catarrhalis between children with community-acquired pneumonia with and without radiological confirmation. ConclusionsAmong children with clinical diagnosis of community-acquired pneumonia submitted to chest radiograph, those with radiologically confirmed pneumonia present a higher rate of infection by S. pneumoniae when compared with those with a normal chest radiograph." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "ObjetivosO objetivo deste estudo foi avaliar o papel do raio-X de tórax na identificação de casos de pneumonia adquirida na comunidade (PAC) causada por agentes bacterianos. MétodosA frequência de infecção por Streptococcus pneumoniae, Haemophilus influenzae e Moraxella catarrhalis em crianças com PAC não hospitalizadas foi comparada com a presença de confirmação radiológica da pneumonia (n=249 crianças com pneumonia radiologicamente confirmada e 366 crianças com raio X de tórax normal). Infecção por S. pneumoniae foi diagnosticada com base na resposta sorológica a pelo menos uma dentre oito proteínas pneumocócicas investigadas (aumento ≥2 vezes nos níveis de IgG em relação a Ply, CbpA, PspA1 e 2, PhtD, StkP-C e PcsB-N ou aumento≥1,5 vezes em relação aPcpA). Infecção por H. influenzae e M. catarrhalis foi definida por aumento≥2 vezes nos níveis de IgG específica a antígenos de cada agente. ResultadosCrianças com pneumonia radiologicamente confirmada apresentaram maior taxa de infecção pelo pneumococo. Além disso, a presença de infecção pneumocócica foi um fator preditor de pneumonia radiologicamente confirmada, aumentando sua chance de detecção em 2,8 vezes (IC 95%: 1,8-4,3). O valor preditivo negative do raio X normal para a infecção por S. pneumoniae foi 86,3% (IC95%: 82,4%-89,7%). Não houve diferença nas frequências de infecção por H. influenzae e M. catarrhalis entre crianças com PAC com ou sem confirmação radiológica. ConclusõesCrianças com diagnóstico clínico de PAC submetidas a um raio X de tórax que apresentam confirmação radiológica tem maior taxa de infecção por S. pneumoniae, comparado às crianças com raio X normal." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Andrade DC, Borges IC, Vilas-Boas AL, Fontoura MS, Araújo-Neto CA, Andrade SC, et al. Infection by Streptococcus pneumoniae in children with or without radiologically confirmed pneumonia. J Pediatr (Rio J). 2018;94:23–30." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2426 "Ancho" => 2427 "Tamanyo" => 307564 ] ] "descripcion" => array:1 [ "en" => "Flow-chart showing inclusion/exclusion criteria for children included in this study." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Radiologically confirmed pneumonia<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>n=249 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Normal chest radiograph<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>n=366 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ply \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">152 (69–277.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">119.5 (60.8–231) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.023 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CbpA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5623 (1422.5–9903.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3316 (650–9540.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.010 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PspA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">318 (119.5–933.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">278.5 (88.8–809.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.113 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PcpA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1077 (303–1941.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">713.5 (152.8–1643) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PhtD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2244 (547–4471.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1447 (404.5–3353) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.015 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">StkB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">299 (98–865.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">274 (82–663) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.116 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PcsB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2215 (478.5–5546) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1682 (349.75–4064) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.016 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H. influenzae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">152 (90–273.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">128 (87–219.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.047 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M. catarrhalis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">104 (69–153.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">114 (81–182) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2405921.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Results area presented as median (interquartile range)." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Data evaluated by Mann–Whitney's U test." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of the median fluorescence intensity (MFI) values from the first serum sample from children with radiologically confirmed pneumonia or those with a normal chest radiograph, using a 1:1600 dilution factor." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Radiologically confirmed pneumonian=249 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Normal chest radiographn=366 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p<a class="elsevierStyleCrossRef" href="#tblfn0020">b</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ply \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (5.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (2.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.042 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CbpA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (7.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (4.1%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.060 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PspA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (5.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (3.8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.407 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PcpA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 (21.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32 (8.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PhtD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 (9.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (1.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">StkB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (8.4%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (2.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PcsB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36 (14.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (1.9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">S. pneumoniae<a class="elsevierStyleCrossRef" href="#tblfn0015">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 (28.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">50 (13.7%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H. influenzae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (7.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (5.2%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.297 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M. catarrhalis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (1.6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (2.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.471 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2405919.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "Antibody response against at least one pneumococcal protein." ] 1 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "b" "nota" => "Data evaluated using chi-square for Fisher's exact test as appropriate." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of the frequencies of antibody response against protein antigens for children with a clinical diagnosis of CAP and either radiologically confirmed pneumonia or a normal chest radiograph." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Radiologically confirmed pneumonia<a class="elsevierStyleCrossRef" href="#tblfn0025">a</a>n=249 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Normal chest radiograph<a class="elsevierStyleCrossRef" href="#tblfn0025">a</a>n=366 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p<a class="elsevierStyleCrossRef" href="#tblfn0030">b</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ply \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">147 (70–257.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">118 (58.8–226.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.009 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CbpA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6226 (1514.5–10656) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3288.5 (616.8–8978.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PspA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">309 (112–909.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">243 (93.8–670.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.049 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PcpA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1149 (418–2240.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">720.5 (150.3–1654) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PhtD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2241 (645–5094.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1486.5 (401.3–3278) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">StkB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">333 (105.5–856) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">253.5 (83.8–679.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.034 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PcsB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2875 (682.5–6051.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1632 (318.8–4304.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H. influenzae \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">160 (94–306) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">139 (92.8–221) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.028 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">M. catarrhalis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95 (69–136.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">109.5 (79–166.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2405920.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "a" "nota" => "Results area presented as median (interquartile range)." ] 1 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "b" "nota" => "Data evaluated by Mann–Whitney U's test." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of the median fluorescence intensity (MFI) values from the second serum sample from children with radiologically confirmed pneumonia or those with a normal chest radiograph, using a 1:1600 dilution factor." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/00217557/0000009400000001/v2_202010230715/S0021755716302455/v2_202010230715/en/main.assets" "Apartado" => array:4 [ "identificador" => "10179" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/00217557/0000009400000001/v2_202010230715/S0021755716302455/v2_202010230715/en/main.pdf?idApp=UINPBA000049&text.app=https://jped.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755716302455?idApp=UINPBA000049"]

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Original article

Infecção por Streptococcus pneumoniae em crianças com ou sem pneumonia radiologicamente confirmada

Dafne C. Andradea,

Corresponding author

andradedafne@yahoo.com.br

Corresponding author.

, Igor C. Borgesa, Ana Luísa Vilas-Boasa, Maria S.H. Fontourab, César A. Araújo-Netoc, Sandra C. Andraded, Rosa V. Brimc, Andreas Meinkee, Aldina Barralf,g, Olli Ruuskanenh, Helena Käyhtyi, Cristiana M. Nascimento-Carvalhoa,b

a Universidade Federal da Bahia (UFBA), Faculdade de Medicina, Programa de Pós-Graduação em Ciências da Saúde, Salvador, BA, Brazil

b Universidade Federal da Bahia (UFBA), Faculdade de Medicina, Departamento de Pediatria, Salvador, BA, Brazil

c Universidade Federal da Bahia (UFBA), Faculdade de Medicina, Departamento de Medicina Interna e Apoio Diagnóstico, Salvador, BA, Brazil

d Universidade Federal da Bahia (UFBA), Complexo Hospitalar Professor Edgard Santos (HUPES), Salvador, BA, Brazil

e Valneva Austria GmbH, Campus Vienna Biocenter 3, Vienna, Austria

f Universidade Federal da Bahia (UFBA), Faculdade de Medicina, Departamento de Patologia, Salvador, BA, Brazil

g Centro de Pesquisa Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, BA, Brazil

h Turku University and University Hospital, Department of Pediatrics, Turku, Finland

i National Institute for Health and Welfare, Helsinki, Finland

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      "pt" => array:1 [
        "titulo" => "Infec&#231;&#227;o por <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> em crian&#231;as com ou sem pneumonia radiologicamente confirmada"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow-chart showing inclusion&#47;exclusion criteria for children included in this study&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Community acquired-pneumonia &#40;CAP&#41; is an important cause of morbidity and mortality in childhood&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> However&#44; the etiologic diagnosis of CAP is challenging&#46; Chest radiographs have been used as a diagnostic tool by the identification of radiologic patterns suggestive of an inflammatory process&#44; such as pulmonary infiltrates&#46; Nevertheless&#44; the role of chest radiograph in pediatric CAP remains controversial&#44; due to problems observed in the routine use of this exam&#44; such as poor inter-observer concordance<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> and the inability to distinguish between distinct etiologic agents&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4</span></a> In turn&#44; a significant proportion of children with a clinical diagnosis of CAP present normal chest radiograph upon admission&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> and important differences in admission and evolution have been reported among children with CAP with or without radiological confirmation&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#8211;9</span></a> Altogether&#44; these data suggest that the disease in children with or without radiologically confirmed pneumonia might be caused by distinct mechanisms and&#47;or different etiologic agents&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In Brazil&#44; <span class="elsevierStyleItalic">Streptococcus pneumoniae</span>&#44; <span class="elsevierStyleItalic">Haemophilus influenzae</span>&#44; and <span class="elsevierStyleItalic">Moraxella catarrhalis</span> have been reported as important bacterial agents of pediatric pneumonia in hospitalized children&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> Herein&#44; the presence of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#44; <span class="elsevierStyleItalic">H&#46; influenzae</span>&#44; and <span class="elsevierStyleItalic">M&#46; catarrhalis</span> was investigated in non-hospitalized Brazilian children aged 2&#8211;59 months with clinical diagnosis of pneumonia with or without radiological confirmation&#46; In doing so&#44; the authors aimed to evaluate the role of the chest radiograph to identify probable cases of CAP caused by typical bacteria&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design and participants</span><p id="par0015" class="elsevierStylePara elsevierViewall">This prospective cohort study was part of a clinical trial that evaluated the use of oral amoxicillin given thrice or twice daily to 2&#8211;59 months-old children diagnosed with CAP &#40;PNEUMOPAC-Efficacy trial&#44; ClinicalTrials&#46;gov <a href="ctgov:NCT01200706">NCT01200706</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a> In that trial&#44; 820 children were enrolled in the Emergency Department of the Universidade Federal da Bahia&#44; in Salvador&#44; Northeast Brazil&#44; from November 2006 to May 2011&#46; All children had a chest radiograph &#40;frontal and lateral views&#41; taken on admission&#44; and blood samples were collected both at admission and at the follow-up visit&#44; two to four weeks later&#46; Inclusion criteria comprised the report of respiratory complaints and detection of lower respiratory findings&#44; along with the presence of pulmonary infiltrate&#47;consolidation on the chest radiograph according to the interpretation of the pediatrician on duty&#46; Legal guardians of the included patients signed an informed consent upon enrollment&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">All chest radiographs were independently read by two pediatric radiologists &#40;CAA-N and SCA&#41;&#44; who were blinded to the clinical data&#46; An overall agreement of 78&#46;7&#37; by these two pediatric radiologists was previously demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> If there was no concordance on the final diagnosis of any exam&#44; this chest radiograph was then evaluated by a third radiologist &#40;RVB&#41;&#46; The radiologic findings were registered according to the standardized interpretation for epidemiological studies previously published by the World Health Organization&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> Radiologically confirmed pneumonia was defined as the presence of pulmonary infiltrate or consolidation in two independent assessments&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The use of pneumococcal conjugate vaccine-10 &#40;PCV10&#41; was universally implemented in Salvador&#44; Brazil&#44; in July 2010&#44; for children aged &#60;2 years&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> Every child included in the PNEUMOPAC-efficacy trial who could have received PCV10 had the vaccine card checked personally by one of the researchers &#40;ICB&#41; after the trial was completed&#46; Patients who received any dose of PCV10 and those whose vaccine status could not be identified were excluded from this analysis&#46; Patients with severe malnutrition&#44; defined as <span class="elsevierStyleItalic">Z</span>-score for weight-for-age under &#8722;3&#46;00&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> were also excluded&#46; Nutritional evaluation was performed using the Anthro software&#46; Children with lower-chest in-drawing or danger signs &#40;inability to drink&#44; convulsions&#44; central cyanosis&#44; grunting in a calm child&#41; were excluded from the PNEUMOPAC-efficacy trial&#44; as well as those with underlying chronic diseases&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">This study was approved by the Ethics Committee of the Universidade Federal da Bahia and was conducted in accordance with the principles of the Declaration of Helsinki&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Laboratory procedures</span><p id="par0035" class="elsevierStylePara elsevierViewall">Fluorescent multiplexed bead-based immunoassay was used to quantify the levels of antibodies against protein antigens from <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#44; <span class="elsevierStyleItalic">H&#46; influenzae</span> and <span class="elsevierStyleItalic">M&#46; catarrhalis</span> using Luminex xMAP&#174; technology &#40;Luminex Corporation&#44; TX&#44; USA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> This assay included eight recombinant proteins from <span class="elsevierStyleItalic">S&#46; pneumoniae</span> &#40;pneumolysin &#91;Ply&#93;&#44; choline binding protein A &#91;CbpA&#93;&#44; pneumococcal surface protein A families 1 and 2 &#91;PspA1 and PspA2&#93;&#44; pneumococcal choline binding protein A &#91;PcpA&#93;&#44; pneumococcal histidine triad protein D &#91;PhtD&#93;&#44; serine&#47;threonine protein kinase &#91;StkP-C&#44; SP1732-3&#93;&#44; and protein required for cell wall separation of group B streptococcus &#91;PcsB-N&#44; SP2216-1&#93;&#41;&#44; three recombinant proteins from <span class="elsevierStyleItalic">H&#46; influenzae</span> &#40;NTHi Protein D&#44; NTHi0371-1&#44; and NTHi0830&#41;&#44; and five recombinant proteins from <span class="elsevierStyleItalic">M&#46; catarrhalis</span> &#40;MC Omp CD&#44; MC&#95;RH4&#95;2506&#44; MC&#95;RH4&#95;1701&#44; MC&#95;RH4&#95;3729-1&#44; and MC&#95;RH4&#95;4730&#41;&#46; Nine bead sets were created using the aforementioned proteins in the following combination&#58; Ply&#44; CbpA&#44; PcpA&#44; PhtD&#44; StkP-C&#44; and PcsB-N were conjugated in one bead region each&#59; PspA1 and PspA2 were conjugated in the same bead region&#59; and all <span class="elsevierStyleItalic">H&#46; influenzae</span> and all <span class="elsevierStyleItalic">M&#46; catarrhalis</span> proteins were conjugated in one bead region per bacterium&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">This assay provided the mean fluorescence intensity &#40;MFI&#41; values for each antigen and serum evaluated&#46; The MFI value represents an indirect measure of the IgG concentration against the studied antigens&#46; True duplicates were used throughout the procedure and their fluorescence readings were averaged&#46; To ensure the repeatability of the assays&#44; high and low controls were analyzed on each plate&#46; Furthermore&#44; acute and convalescent samples were always analyzed on the same plate&#46; All samples were tested using 1&#58;400 and 1&#58;1600 dilutions and&#44; if necessary&#44; further dilutions were performed&#46; The occurrence of a serological response against <span class="elsevierStyleItalic">S&#46; pneumoniae</span> was defined as an increase in the antibody levels &#8805;2-fold for IgG against Ply&#44; CbpA&#44; PspA1 and PspA2&#44; PhtD&#44; StkP-C&#44; and PcsB-N&#44; or an increase &#8805;1&#46;5-fold for IgG against PcpA&#44; based on the validation of a sensitive and specific serological test for the diagnosis of invasive pneumococcal disease&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> The diagnosis of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> was established by the detection of serological response against any of the evaluated antigens&#44; based on the specificity of the assay and good correlation with ELISA&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> The sensitivity and specificity for a serological response against each antigen were previously published&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> The occurrence of infection by <span class="elsevierStyleItalic">H&#46; Influenzae</span> or <span class="elsevierStyleItalic">M&#46; catarrhalis</span> was defined as an increase in antibody levels &#8805;2-fold between acute and convalescent samples&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">15&#44;17</span></a> All serological tests were performed by DCA and ICB at the National Institute for Health and Welfare&#44; in Helsinki&#44; Finland&#46; The frequency of these infections analyzed by age distribution&#44; interval of sample collection&#44; and duration of disease has been published elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Categorical variables were compared using the chi-squared or Fisher&#39;s exact tests as appropriate&#44; and continuous variables were evaluated using Mann&#8211;Whitney&#39;s <span class="elsevierStyleItalic">U</span> test&#44; as they presented non-parametric distribution&#46; The negative predictive value of the normal chest radiograph for the diagnosis of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> was calculated&#46; Multivariate logistic regression was performed using the presence of radiologically confirmed pneumonia as the dependent variable and infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> as the independent variable&#46; This model was adjusted by age and infection by <span class="elsevierStyleItalic">H&#46; influenzae</span> or <span class="elsevierStyleItalic">M&#46; catarrhalis</span>&#46; All statistical tests were two-tailed&#44; with a significance level of 0&#46;05&#46; The software Stata&#47;SE 12&#46;0 &#40;StataCorp&#46; 2011&#46; <span class="elsevierStyleItalic">Stata Statistical Software&#58; Release 12</span>&#46; College Station&#44; TX&#44; USA&#41; was used to calculate the negative predictive value of the normal chest radiograph&#44; and the software SPSS &#40;SPSS Inc&#46;&#44; version 9&#46;0&#46; Chicago&#44; USA&#41; was used for the remaining analyzes&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">Out of 820 patients included in the PNEUMOPAC-efficacy trial&#44; 615 were included in this study&#44; of whom 249 &#40;40&#46;5&#37;&#41; had radiologically confirmed pneumonia and 366 &#40;59&#46;5&#37;&#41; had normal chest radiograph&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the flowchart of the included and excluded cases in this investigation&#46; Overall&#44; 311 &#40;50&#46;6&#37;&#41; were males and the median age was 27&#46;2 months &#40;25th&#8211;75th percentile&#58; 14&#46;9&#8211;41&#46;4 months&#41;&#46; Consolidation was detected by radiologists 1&#44; 2&#44; and 3 in 84&#46;6&#37;&#44; 79&#46;8&#37;&#44; and 67&#46;3&#37; of the cases with concordant radiologically confirmed pneumonia&#44; respectively&#46; The remaining cases of radiologically confirmed pneumonia were diagnosed based on the detection of pulmonary infiltrates&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The comparison of the levels of antibodies on admission &#40;first serum sample&#41; against the studied antigens using a 1&#58;1600 dilution factor is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Children with radiologically confirmed pneumonia had significantly higher levels of antibodies against several protein antigens from <span class="elsevierStyleItalic">S&#46; pneumoniae</span> and <span class="elsevierStyleItalic">H&#46; influenzae</span>&#44; and lower levels of antibodies against <span class="elsevierStyleItalic">M&#46; catarrhalis</span> proteins&#46; Similar results were obtained when using a 1&#58;400 dilution factor &#40;data not shown&#41;&#46; Children with radiologically confirmed pneumonia also presented a higher frequency of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#46; Antibody responses against <span class="elsevierStyleItalic">S&#46; pneumoniae</span> proteins were detected in 28&#46;5&#37; of the children with radiologically confirmed pneumonia and in 13&#46;7&#37; of children with a normal chest radiograph &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Antibody responses against PcpA&#44; PhtD&#44; and PcsB were most frequently detected in children with radiologically confirmed pneumonia&#46; These results are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; When the levels of antibodies against the studied antigens on the second serum sample were compared using a 1&#58;1600 dilution factor&#44; higher levels of IgG against all proteins from <span class="elsevierStyleItalic">S&#46; pneumoniae</span> and <span class="elsevierStyleItalic">H&#46; influenzae</span> were observed&#44; as well as lower levels of antibodies against <span class="elsevierStyleItalic">M&#46; catarrhalis</span>&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Similar results were obtained when using a 1&#58;400 dilution factor &#40;data not shown&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">A multivariate logistic regression was performed to assess the effect of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> on the presence of radiologically confirmed pneumonia&#44; adjusting this model by infection by <span class="elsevierStyleItalic">H&#46; influenzae</span> or <span class="elsevierStyleItalic">M&#46; catarrhalis</span> and age&#46; The presence of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> increased the odds of radiologically confirmed pneumonia by 2&#46;8 &#40;95&#37; CI&#58; 1&#46;8&#8211;4&#46;3&#41;&#46; The presence of infection by either <span class="elsevierStyleItalic">H&#46; influenzae</span> or <span class="elsevierStyleItalic">M&#46; catarrhalis</span> or the age of the child did not affect the odds for detection of radiologically confirmed pneumonia &#40;odds radio &#91;95&#37; CI&#93;&#58; 1&#46;42 &#91;0&#46;7&#8211;2&#46;9&#93;&#59; 0&#46;4 &#91;0&#46;1&#8211;1&#46;6&#93;&#59; and 0&#46;9 &#91;0&#46;9&#8211;1&#93;&#44; respectively&#41;&#46; Furthermore&#44; the negative predictive value of the normal chest radiograph for the diagnosis of infection by the pneumococcus was 86&#46;3&#37; &#40;95&#37; CI&#58; 82&#46;4&#8211;89&#46;7&#37;&#41;&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">This study demonstrated that children with radiologically confirmed pneumonia have a higher frequency of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> than those with a normal chest radiograph&#46; The presence of infection by pneumococcus was independently associated to radiologically confirmed pneumonia among non-hospitalized children with clinical CAP&#46; Furthermore&#44; the presence of a normal chest radiograph had a high negative predictive value for the detection of antibody responses against <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">A higher frequency of antibody response against several antigens from <span class="elsevierStyleItalic">S&#46; pneumoniae</span> was observed in the group of children with radiologically confirmed pneumonia when compared with those with a normal chest radiograph&#46; This finding corroborates the results from previous studies&#44; which demonstrated that the presence of alveolar infiltrates on chest radiographs was associated with bacterial pneumonia&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> For instance&#44; Nascimento-Carvalho et al&#46; also reported that infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> was more frequently detected among hospitalized children with CAP who presented radiographic pneumonia rather than those with a normal chest radiograph&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> In turn&#44; children with a normal chest radiograph had a higher incidence of viral infection&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> This is the first report of the association between pneumococcal infection and radiologically confirmed pneumoniae among non-hospitalized children with clinical CAP&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Accordingly&#44; the negative predictive value of the normal chest radiograph for the detection of pneumococcal infection was high &#40;86&#46;3&#37; &#91;95&#37; CI&#58; 82&#46;4&#8211;89&#46;7&#37;&#93;&#41;&#46; Although an association between bacterial infection and alveolar infiltrates&#47;consolidation has been previously described&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> these findings cannot reliably establish the etiologic diagnosis of CAP&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;5</span></a> Therefore&#44; the present finding that the normal chest radiograph has a high negative predictive value for pneumococcal infection may aid in the interpretation of this exam&#46; The high negative predictive value observed for the normal chest radiograph in a population with high prevalence of pneumococcal infection is noteworthy&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> thereby reinforcing the present results&#46; Altogether&#44; the present data indicate that children with non-severe CAP with radiologically confirmed pneumonia have a higher chance of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#44; whereas children with a normal chest radiograph are not likely to present infection by this agent and might not benefit from empiric antibiotic therapy&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Data from vaccine trials reinforce the relationship between pneumococcal infection and radiologically confirmed pneumonia&#44; as a differential effect of pneumococcal vaccination was found on the rates of pediatric CAP depending on the applied diagnostic criteria&#46; For instance&#44; the efficacy of the PCV10 was significantly higher for children with consolidation on the chest radiograph than for children either with alveolar infiltrates or solely with a clinical diagnosis of CAP&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> Therefore&#44; the greater impact of pneumococcal vaccination on children with consolidation on chest radiographs suggests that patients with this radiological diagnosis present a higher incidence of pneumococcal infection&#46; These findings are consistent with those reported by Lucero et al&#46;&#44; who demonstrated a good vaccine efficacy of PCV11 on children with radiographic pneumonia defined as consolidation and a practicably negligible vaccine efficacy for children with a clinical diagnosis of pneumonia&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> These vaccine trials provide indirect evidence regarding the etiology of pneumonia in children with distinct radiological patterns&#44; indicating that children with radiologically confirmed pneumonia indeed present a higher frequency of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The role of the chest radiograph in the management of children with CAP&#44; however&#44; has been largely debated&#46; Importantly&#44; Bradley et al&#46; recommend that the chest radiograph should only be used in children who are hospitalized or with hypoxemia&#44; significant respiratory distress&#44; suspected complications&#44; or therapy failure&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> This position is corroborated by Harris et al&#46;&#44; who stated that children with signs and symptoms suggesting pneumonia who are not admitted to hospital should not routinely have a chest radiograph&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> These recommendations are partly due to previous studies that have shown that bacterial pneumonia cannot be differentiated from non-bacterial pneumonia based solely on the findings of an abnormal chest radiograph&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;4&#44;24</span></a> Furthermore&#44; the current evidence suggests that the use of a chest radiograph does not improve the outcome of pediatric patients with CAP&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> Nonetheless&#44; it is important to emphasize that when the impact of the chest radiograph on the management of children with CAP was evaluated&#44; the patients received antibiotics at the discretion of the attending physician&#44; regardless of the radiologic findings&#44; thereby limiting the potential benefit of a radiological study in these patients as a diagnostic tool with therapeutic implications&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> Accordingly&#44; Harris et al&#46; recommend the use of antibiotics for all children with a clear diagnosis of CAP&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> Both guidelines agree&#44; however&#44; that young children do not require routine use of antibiotics&#44; as most present viral acute lower respiratory infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">22&#44;23</span></a> In this scenario&#44; although the chest radiograph does not unequivocally distinguish etiologic agents of CAP&#44; it may help differentiating distinct patterns of lower respiratory infections&#46; Recent evidence has demonstrated important differences between children with or without radiologically confirmed pneumonia in the clinical presentation and evolution&#46; Children with radiologically confirmed pneumonia have a higher frequency and longer persistence of fever&#44;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#8211;8</span></a> and also evolve more severely&#44; with longer hospitalization&#44; higher need of respiratory support&#44; and higher rates of treatment failure&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> These differences indicate that children with and without radiologically confirmed pneumonia may have different patterns of lower respiratory tract infection&#44; and the chest radiograph&#44; when performed&#44; may aid the management of doubtful cases of non-severe CAP&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">It was also observed that children with radiologically confirmed pneumonia had higher levels of antibodies against several pneumococcal proteins both at admission and in convalescence&#46; Lower levels of anti-pneumococcal antibodies on admission have been associated with a higher frequency of antibody responses against <span class="elsevierStyleItalic">S&#46; pneumoniae</span> due to particularities of the serological methods&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> Therefore&#44; the level of antibodies at admission probably was not responsible for the higher rate of antibody responses against the pneumococcus in children with radiological pneumonia&#46; The higher level of antibodies at admission in this group of children&#44; in turn&#44; might have been caused by previous colonization by <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#46; Nasopharyngeal colonization has been recognized as part of the natural history of pneumococcal disease&#44; which ensues if immunological barriers are crossed by the colonizing bacteria&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> Also&#44; children with clinical and radiological pneumonia are also more frequently colonized with <span class="elsevierStyleItalic">S&#46; pneumoniae</span> when compared with healthy controls&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> Therefore&#44; it is possible that a higher rate of carriage of <span class="elsevierStyleItalic">S&#46; pneumoniae</span> in children with radiologically confirmed pneumonia elicited the higher levels of anti-pneumococcal antibodies found in this subgroup&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">No difference was observed on the rates of antibody response against <span class="elsevierStyleItalic">H&#46; influenzae</span> and <span class="elsevierStyleItalic">M&#46; catarrhalis</span> in this study&#44; possibly due to the low numbers of responders within the study group&#46; However&#44; discretely higher levels of antibodies against <span class="elsevierStyleItalic">H&#46; influenzae</span> were found in children with radiologically confirmed pneumonia&#44; as well as lower levels of antibodies against <span class="elsevierStyleItalic">M&#46; catarrhalis</span>&#46; It is known that several bacterial agents compete to colonize the nasopharyngeal tract of pediatric patients&#44; creating a dynamic process of turnover of colonizing agents&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> Increased rates of colonization by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> might also have contributed to lower the levels of antibodies against <span class="elsevierStyleItalic">M&#46; catarrhalis</span> on the samples collected from children with radiologically confirmed pneumonia at admission&#46; In turn&#44; a positive correlation between colonization by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> and <span class="elsevierStyleItalic">H&#46; influenzae</span> has already been described&#44; which may have contributed to the high levels of antibodies at admission found against <span class="elsevierStyleItalic">H&#46; influenzae</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The limitations of the present study must be emphasized&#46; Firstly&#44; data on the colonization status of the evaluated children were not available&#44; and the putative effect of pneumococcal carriage on the antibody levels at admission was not evaluated&#46; Secondly&#44; the study was composed of unvaccinated children&#44; which does not represent the reality in most countries in the post-PCV era&#46; Nevertheless&#44; recent evidence suggests that the use of PCV does not interfere with the result of protein-based serological assays in children with CAP&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> which favors the generalization of the present results&#46; Also&#44; data on the use of other vaccines that could have influenced the results presented herein&#44; such as the <span class="elsevierStyleItalic">H&#46; influenzae</span> type b vaccine&#44; was not available&#46; However&#44; the coverage of the <span class="elsevierStyleItalic">H&#46; influenzae</span> type b vaccine among the pediatric population in Brazil is high &#40;&#62;80&#37;&#41;&#44; so differential rates of vaccination probably did not affect the present results&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> Finally&#44; as all antigens from <span class="elsevierStyleItalic">H&#46; influenzae</span> and <span class="elsevierStyleItalic">M&#46; catarrhalis</span> were conjugated in one bead region per bacterium&#44; individual fluorescence readings were not obtained for these antigens&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In conclusion&#44; this study demonstrated that&#44; among non-hospitalized children with clinical CAP who were submitted to a chest radiograph&#44; those with radiologically confirmed pneumonia had a higher frequency of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> compared to children with a normal chest radiograph&#46; Furthermore&#44; the presence of pneumococcal infection was independently associated with radiologically confirmed pneumonia&#59; normal chest radiograph has a high negative predictive value for pneumococcal infection&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">Sanofi Pasteur &#40;Lyon&#44; France&#41; supplied PcpA and PhtD&#59; Prof&#46; Elaine Tuomanen at St&#46; Judes Children&#39;s Research Hospital &#40;Memphis&#44; United States&#41; supplied Ply&#44; CbpA&#44; PspA1&#59; Profs&#46; Susan Hollingshead&#44; David Briles&#44; and Pat Coan at University of Alabama &#40;Birmingham&#44; United States&#41; supplied PspA2&#59; and Valneva Austria GmbH &#40;Vienna&#44; Austria&#41; supplied StkP-C&#44; PcsB-N&#44; NTHi Protein D&#44; NTHi0371-1&#44; NTHi0830&#44; MC Omp CD&#44; MC&#95;RH4&#95;2506&#44; MC&#95;RH4&#95;1701&#44; MC&#95;RH4&#95;3729-1&#44; and MC&#95;RH4&#95;4730&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">This work was supported by the Bahia State Agency for Research Funding &#40;<span class="elsevierStyleGrantSponsor" id="gs1">Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado da Bahia</span> &#91;FAPESB&#93;&#41; and the Brazilian Council for Scientific and Technological Development &#40;<span class="elsevierStyleGrantSponsor" id="gs2">Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico</span> &#91;CNPq&#93;&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">Andreas Meinke is an employee of Valneva Austria GmbH&#46; The others authors declare no conflicts of interest&#46;</p></span></span>"
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    "fechaRecibido" => "2016-10-30"
    "fechaAceptado" => "2017-01-30"
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          "palabras" => array:5 [
            0 => "Bacterial infection"
            1 => "Etiology"
            2 => "Lower respiratory tract infection"
            3 => "Radiological study"
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            0 => "Infec&#231;&#227;o bacteriana"
            1 => "Etiologia"
            2 => "Infec&#231;&#227;o do trato respirat&#243;rio inferior"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Community-acquired pneumonia is an important cause of morbidity in childhood&#44; but the detection of its causative agent remains a diagnostic challenge&#46; The authors aimed to evaluate the role of the chest radiograph to identify cases of community-aquired pneumonia caused by typical bacteria&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The frequency of infection by <span class="elsevierStyleItalic">Streptococcus pneumoniae</span>&#44; <span class="elsevierStyleItalic">Haemophilus influenzae</span>&#44; and <span class="elsevierStyleItalic">Moraxella catarrhalis</span> was compared in non-hospitalized children with clinical diagnosis of community acquired pneumonia aged 2&#8211;59 months with or without radiological confirmation &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>249 and 366&#44; respectively&#41;&#46; Infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> was diagnosed by the detection of a serological response against at least one of eight pneumococcal proteins &#40;defined as an increase &#8805;2-fold in the IgG levels against Ply&#44; CbpA&#44; PspA1 and PspA2&#44; PhtD&#44; StkP-C&#44; and PcsB-N&#44; or an increase &#8805;1&#46;5-fold against PcpA&#41;&#46; Infection by <span class="elsevierStyleItalic">H&#46; influenzae</span> and <span class="elsevierStyleItalic">M&#46; catarrhalis</span> was defined as an increase &#8805;2-fold on the levels of microbe-specific IgG&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Children with radiologically confirmed pneumonia had higher rates of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#46; The presence of pneumococcal infection increased the odds of having radiologically confirmed pneumonia by 2&#46;8 times &#40;95&#37; CI&#58; 1&#46;8&#8211;4&#46;3&#41;&#46; The negative predictive value of the normal chest radiograph for infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> was 86&#46;3&#37; &#40;95&#37; CI&#58; 82&#46;4&#8211;89&#46;7&#37;&#41;&#46; There was no difference on the rates of infection by <span class="elsevierStyleItalic">H&#46; influenzae</span> and <span class="elsevierStyleItalic">M&#46; catarrhalis</span> between children with community-acquired pneumonia with and without radiological confirmation&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Among children with clinical diagnosis of community-acquired pneumonia submitted to chest radiograph&#44; those with radiologically confirmed pneumonia present a higher rate of infection by <span class="elsevierStyleItalic">S&#46; pneumoniae</span> when compared with those with a normal chest radiograph&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">O objetivo deste estudo foi avaliar o papel do raio-X de t&#243;rax na identifica&#231;&#227;o de casos de pneumonia adquirida na comunidade &#40;PAC&#41; causada por agentes bacterianos&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A frequ&#234;ncia de infec&#231;&#227;o por <span class="elsevierStyleItalic">Streptococcus pneumoniae&#44; Haemophilus influenzae</span> e <span class="elsevierStyleItalic">Moraxella catarrhalis</span> em crian&#231;as com PAC n&#227;o hospitalizadas foi comparada com a presen&#231;a de confirma&#231;&#227;o radiol&#243;gica da pneumonia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>249 crian&#231;as com pneumonia radiologicamente confirmada e 366 crian&#231;as com raio X de t&#243;rax normal&#41;&#46; Infec&#231;&#227;o por <span class="elsevierStyleItalic">S&#46; pneumoniae</span> foi diagnosticada com base na resposta sorol&#243;gica a pelo menos uma dentre oito prote&#237;nas pneumoc&#243;cicas investigadas &#40;aumento &#8805;2 vezes nos n&#237;veis de IgG em rela&#231;&#227;o a Ply&#44; CbpA&#44; PspA1 e 2&#44; PhtD&#44; StkP-C e PcsB-N ou aumento&#8805;1&#44;5 vezes em rela&#231;&#227;o aPcpA&#41;&#46; Infec&#231;&#227;o por <span class="elsevierStyleItalic">H&#46; influenzae</span> e <span class="elsevierStyleItalic">M&#46; catarrhalis</span> foi definida por aumento&#8805;2 vezes nos n&#237;veis de IgG espec&#237;fica a ant&#237;genos de cada agente&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Crian&#231;as com pneumonia radiologicamente confirmada apresentaram maior taxa de infec&#231;&#227;o pelo pneumococo&#46; Al&#233;m disso&#44; a presen&#231;a de infec&#231;&#227;o pneumoc&#243;cica foi um fator preditor de pneumonia radiologicamente confirmada&#44; aumentando sua chance de detec&#231;&#227;o em 2&#44;8 vezes &#40;IC 95&#37;&#58; 1&#44;8-4&#44;3&#41;&#46; O valor preditivo negative do raio X normal para a infec&#231;&#227;o por <span class="elsevierStyleItalic">S&#46; pneumoniae</span> foi 86&#44;3&#37; &#40;IC95&#37;&#58; 82&#44;4&#37;-89&#44;7&#37;&#41;&#46; N&#227;o houve diferen&#231;a nas frequ&#234;ncias de infec&#231;&#227;o por <span class="elsevierStyleItalic">H&#46; influenzae</span> e <span class="elsevierStyleItalic">M&#46; catarrhalis</span> entre crian&#231;as com PAC com ou sem confirma&#231;&#227;o radiol&#243;gica&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Crian&#231;as com diagn&#243;stico cl&#237;nico de PAC submetidas a um raio X de t&#243;rax que apresentam confirma&#231;&#227;o radiol&#243;gica tem maior taxa de infec&#231;&#227;o por <span class="elsevierStyleItalic">S&#46; pneumoniae</span>&#44; comparado &#224;s crian&#231;as com raio X normal&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Please cite this article as&#58; Andrade DC&#44; Borges IC&#44; Vilas-Boas AL&#44; Fontoura MS&#44; Ara&#250;jo-Neto CA&#44; Andrade SC&#44; et al&#46; Infection by <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> in children with or without radiologically confirmed pneumonia&#46; J Pediatr &#40;Rio J&#41;&#46; 2018&#59;94&#58;23&#8211;30&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow-chart showing inclusion&#47;exclusion criteria for children included in this study&#46;</p>"
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                  \t\t\t\t">152 &#40;69&#8211;277&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">119&#46;5 &#40;60&#46;8&#8211;231&#41;&nbsp;\t\t\t\t\t\t\n
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                      "titulo" => "Global&#44; regional&#44; and national causes of child mortality in 2000&#8211;13&#44; with projections to inform post-2015 priorities&#58; an updated systematic analysis"
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                    0 => array:2 [
                      "doi" => "10.1111/j.1651-2227.2008.00789.x"
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                        "tituloSerie" => "Acta Paediatr"
                        "fecha" => "2008"
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                        "paginaInicial" => "943"
                        "paginaFinal" => "947"
                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18422803"
                            "web" => "Medline"
                          ]
                        ]
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0125" class="elsevierStylePara elsevierViewall">The authors would like thank Sanofi Pasteur &#40;Lyon&#44; France&#41; for supplying PcpA and PhtD&#59; Prof&#46; Elaine Tuomanen at St&#46; Judes Children&#39;s Research Hospital &#40;Memphis&#44; United States&#41; for supplying Ply&#44; CbpA&#44; PspA1&#59; Profs&#46; Susan Hollingshead&#44; David Briles&#44; and Pat Coan at University of Alabama &#40;Birmingham&#44; United States&#41;&#44; for supplying PspA2&#59; and Valneva Austria GmbH &#40;Vienna&#44; Austria&#41; for supplying SP1732-3&#44; SP2216-1&#44; NTHi Protein D&#44; NTHi0371-1&#44; NTHi0830&#44; MC Omp CD&#44; MC&#95;RH4&#95;2506&#44; MC&#95;RH4&#95;1701&#44; MC&#95;RH4&#95;3729-1&#44; and MC&#95;RH4&#95;4730&#46;</p>"
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Article information

ISSN: 00217557
Original language: English

DOI:10.1016/j.jped.2017.03.004

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Year/Month	Html	Pdf	Total

2024 November	3	2	5
2024 October	19	25	44
2024 September	23	36	59
2024 August	54	37	91
2024 July	54	40	94
2024 June	39	16	55
2024 May	16	5	21
2024 April	33	25	58
2024 March	30	19	49
2024 February	27	26	53
2024 January	29	27	56
2023 December	8	21	29
2023 November	20	34	54
2023 October	24	30	54
2023 September	29	42	71
2023 August	15	14	29
2023 July	19	14	33
2023 June	10	8	18
2023 May	26	15	41
2023 April	19	20	39
2023 March	38	19	57
2023 February	15	16	31
2023 January	23	17	40
2022 December	48	32	80
2022 November	27	17	44
2022 October	49	32	81
2022 September	32	29	61
2022 August	29	32	61
2022 July	52	50	102
2022 June	27	32	59
2022 May	20	28	48
2022 April	63	34	97
2022 March	38	35	73
2022 February	24	20	44
2022 January	16	20	36
2021 December	12	20	32
2021 November	11	14	25
2021 October	10	22	32
2021 September	10	19	29
2021 August	7	11	18
2021 July	10	12	22
2021 June	7	10	17
2021 May	12	15	27
2021 April	15	14	29
2021 March	13	12	25
2021 February	10	13	23
2021 January	10	13	23
2020 December	14	8	22
2020 November	10	12	22
2020 October	8	5	13
2020 September	14	11	25
2020 August	6	2	8
2020 July	5	6	11
2020 June	9	4	13
2020 May	11	8	19
2020 April	13	9	22
2020 March	6	2	8
2020 February	11	15	26
2020 January	11	15	26
2019 December	8	6	14
2019 November	9	8	17
2019 October	12	14	26
2019 September	7	9	16
2019 August	15	6	21
2019 July	16	7	23
2019 June	11	19	30
2019 May	11	4	15
2019 April	20	13	33
2019 March	16	12	28
2019 February	14	5	19
2019 January	12	10	22
2018 December	17	7	24
2018 November	64	3	67
2018 October	91	11	102
2018 September	17	8	25
2018 August	9	3	12
2018 July	9	6	15
2018 June	17	4	21
2018 May	48	9	57
2018 April	9	2	11
2018 March	48	17	65
2018 February	46	22	68
2018 January	17	15	32
2017 December	1	1	2
2017 November	0	5	5
2017 October	3	5	8
2017 September	0	6	6
2017 August	1	13	14
2017 July	0	13	13

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