Systemic cytokines/chemokines associated to radiographic abnormalities in pneumonia in children.

Community-acquired pneumonia (CAP) diagnosis remains a challenge in paediatrics. Chest radiography is considered gold standard for definition of pneumonia, however no previous study assessed the relationship between immune response and radiographic-confirmed-pneumonia. We assessed association between cytokines/chemokines levels and radiographic abnormalities in children with CAP. Children < 5-years-old hospitalized with CAP were investigated in a prospective study at the Federal University of Bahia Hospital, Brazil. On admission, clinical data and biological samples were collected to investigate 20 aetiological agents and determine serum cytokines/chemokines levels; chest radiographs were performed. Among 158 patients, radiographic diagnosis of pneumonia was confirmed in 126(79.7%) and 17(10.8%) had pleural effusion. Viral, bacterial and pneumococcal infection were detected in 80(50.6%), 78(49.4%) and 37(23.4%) cases. By comparing the median concentrations of serum cytokines/chemokines between children with or without pleural effusion, interleukin(IL)-6 was higher (26.6[18.6-103.7] vs 3.0[0.0-19.8]; p < 0.001) among those with pleural effusion; and between children with or without radiographic-confirmed-pneumonia, IL-6 was higher in the first subgroup (4.5[0.0-23.4] vs 0.0[0.0-3.6]; p = 0.02) after having excluded cases with pleural effusion. Stratified analyses according to aetiology showed IL-6 increase in the radiographic-confirmed-pneumonia subgroup inside the pneumococcal infection (28.2[5.9-64.1] vs 0.0[0.0-0.0]; p = 0.03) subgroup. By multivariable analysis, with IL-6 as dependent variable, pneumococcal infection and pleural effusion showed independent association with IL-6 elevation [respective OR: 5.071 (95%CI = 2.226-11.548; p < 0.001) and 13.604 (95%CI = 3.463-53.449; p = 0.0001)]. Considering the cases without pleural effusion, the area under the curve of IL-6 to predict pneumococcal infection was 0.76 (95%CI = 0.66-0.86; p < 0.001). IL-6 increase is a potential biomarker of pneumococcal infection among children with CAP without pleural effusion upon admission.

Infection by Streptococcus pneumoniae in children with or without radiologically confirmed pneumonia / Infecção por Streptococcus pneumoniae em crianças com ou sem pneumonia radiologicamente confirmada

Abstract Objective: Community-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. Methods: The 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. Results: Children 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. Conclusions: Among 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.

Resumo Objetivo: Avaliar o papel do raios X de tórax na identificação de casos de pneumonia adquirida na comunidade (PAC) causada por agentes bacterianos. Métodos: A 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 raios 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 vez 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. Resultados: Crianças 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, o que aumenta sua chance de detecção em 2,8 vezes (IC 95%: 1,8-4,3). O valor preditivo negativo do raios 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. Conclusão: Crianças com diagnóstico clínico de PAC submetidas a um raios X de tórax que apresentam confirmação radiológica têm maior taxa de infecção por S. pneumoniae comparadas com as crianças com raios X normal.

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

OBJECTIVE: Community-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. METHODS: The 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. RESULTS: Children 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. CONCLUSIONS: Among 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.

Association between bacterial infection and radiologically confirmed pneumonia among children.

BACKGROUND: The role of chest radiograph (CXR) among children with community-acquired pneumonia is controversial. We aimed to assess if there is association between a specific etiology and radiologically confirmed pneumonia. METHODS: This was a prospective cross-sectional study. Based on report of respiratory complaints and fever/difficulty breathing plus the detection of pulmonary infiltrate/pleural effusion on the CXR taken upon admission read by the pediatrician on duty, children <5-year-old hospitalized with community-acquired pneumonia were enrolled. On admission, clinical data and biological samples were collected to investigate 19 etiological agents (11 viruses and 8 bacteria). CXR taken upon admission was independently read by a pediatric radiologist blinded to clinical data. RESULTS: The study group comprised 209 cases with evaluated CXR and establishment of a probable etiology. Radiologically confirmed pneumonia, normal CXR and other radiographic diagnoses were described for 165 (79.0%), 36 (17.2%) and 8 (3.8%) patients, respectively. Viral infection was significantly more common among patients without radiologically confirmed pneumonia (68.2% vs. 47.9%; P = 0.02), particularly among those with normal CXR (66.7% vs. 47.9%; P = 0.04) when compared with patients with radiologically confirmed pneumonia. Bacterial infection was more frequent among cases with radiologically confirmed pneumonia (52.1% vs. 31.8%; P = 0.02). Likewise, pneumococcal infection was more frequently detected among children with radiologically confirmed pneumonia in regard to children with normal CXR (24.2% vs. 8.3%; P = 0.04). Sensitivity (95% confidence interval) of radiologically confirmed pneumonia for pneumococcal infection was 93% (80-98%), and negative predictive value (95% confidence interval) of normal CXR for pneumococcal infection was 92% (77-98%). CONCLUSION: Bacterial infection, especially pneumococcal one, is associated with radiologically confirmed pneumonia.

Comparison of oral amoxicillin given thrice or twice daily to children between 2 and 59 months old with non-severe pneumonia: a randomized controlled trial.

OBJECTIVES: Oral amoxicillin (50 mg/kg/day) thrice daily is the first-line therapy for non-severe childhood pneumonia. Compliance could be enhanced if two daily doses are employed. We assessed the equivalence of oral amoxicillin (50 mg/kg/day) thrice or twice daily in those patients. PATIENTS AND METHODS: This randomized (1 : 1), controlled, triple-blinded investigation conducted at one centre in Brazil included children aged 2-59 months with non-severe pneumonia diagnosed by trained paediatricians based on respiratory complaints and radiographic pulmonary infiltrate/consolidation. Participants were randomly assigned to receive one bottle (Amoxicillin 1) at 6 am, 2 pm and 10 pm and the other bottle (Amoxicillin 2) at 8 am and 8 pm: one bottle contained amoxicillin and the other placebo and vice versa. Only the pharmacist knew patients' allocation. Follow-up assessments were done at 2, 5 and 14 days after enrolment. Chest radiographs were read by three independent radiologists. Primary outcome was treatment failure (development of danger signs, persistence of fever, tachypnoea, development of serious adverse reactions, death and withdrawal from the trial) at 48 h. ClinicalTrials.gov: identifier NCT01200706. RESULTS: Four hundred and twelve and 408 participants received amoxicillin thrice or twice daily, respectively. Treatment failure was detected in 94 (22.8%) and 94 (23.0%) patients in intention-to-treat analysis (risk difference 0.2%; 95% CI: -5.5%-6.0%) and in 80 (20.1%) and 85 (21.3%) patients in per-protocol analysis (risk difference 1.2%; 95% CI: -4.4%-6.8%). Pneumonia was radiologically confirmed by concordant reading in 277 (33.8%) cases, among whom treatment failure was registered in 25/133 (18.8%) and 27/144 (18.8%) participants from the thrice and twice daily doses subgroups, respectively (risk difference -0.05%; 95% CI: -9.3%-9.2%). CONCLUSIONS: Oral amoxicillin (50 mg/kg/day) twice daily is as efficacious as thrice daily.

Chlamydia trachomatis: a major agent of respiratory infections in infants from low-income families.

OBJECTIVES: To determine the prevalence of lower respiratory tract infection (LRTI) due to Chlamydia trachomatis in newborn infants and to describe the clinical, laboratory, and radiological characteristics of the disease. METHODS: A cross-sectional study carried out over a 12-month period. All infants up to 6 months of age admitted consecutively at the Centro Pediátrico Professor Hosannah de Oliveira of the Universidade Federal da Bahia in Salvador, Brazil, and diagnosed with LRTI according to clinical and/or radiological criteria were included in the study. C. trachomatis infection was diagnosed by the enzyme-linked immunosorbent assay (ELISA) for the detection of IgM-class antibodies. The prevalence of LRTI by C. trachomatis was determined and the prevalence ratios for the infection and clinical or laboratory variables were calculated. RESULTS: One hundred and fifty-one infants were submitted to serology for C. trachomatis and 15 (9.9%) tested positive. Chlamydial infection was found only in infants under 5 months of age, mainly in those aged under 2 months. Three of the infants with C. trachomatis infection were born by cesarean section. Conjunctivitis and eosinophilia had occurred in 33.3% of the cases. Chest X rays were abnormal in 92.0% of cases. There was an association between C. trachomatis infection and the duration of hospitalization exceeding 15 days (p = 0.0398) and oxygen therapy (p = 0.0484). CONCLUSIONS: There was a high prevalence of C. trachomatis respiratory infection in the population studied. The infection was associated with a more severe form of the disease, emphasizing the importance of testing pregnant women for this infection to avoid infection in the newborn infant.

Chlamydia trachomatis: um importante agente de infecções respiratórias em lactentes de famílias de baixa renda / Chlamydia trachomatis: a major agent of respiratory infections in infants from low-income families

OBJETIVOS: Determinar a prevalência de infecção do trato respiratório inferior (ITRI) por Chlamydia trachomatis em lactentes internados e descrever as características clínicas, laboratoriais e radiológicas da doença. MÉTODOS: Este foi um estudo do tipo corte transversal, realizado durante um período de 12 meses. Foram incluídos todos os lactentes de até 6 meses internados consecutivamente no Centro Pediátrico Professor Hosannah de Oliveira da Universidade Federal da Bahia, em Salvador, BA, com diagnóstico clínico ou clínico-radiológico de ITRI. O diagnóstico de infecção por C. trachomatis foi realizado através da pesquisa de anticorpos da classe IgM, utilizando-se o ensaio imunoenzimático (ELISA). A prevalência de ITRI por C. trachomatis foi determinada, e foram calculadas as razões de prevalência para essa infecção e variáveis clínicas e laboratoriais. RESULTADOS: Cento e cinquenta e um lactentes realizaram sorologia para C. trachomatis, das quais 15 (9,9%) foram positivas. A infecção por C. trachomatis ocorreu unicamente entre os menores de 5 meses, principalmente naqueles menores de 2 meses. Três crianças com infecção por C. trachomatis nasceram de parto cesáreo. Conjuntivite e eosinofilia ocorreram em 33,3% dos casos. As radiografias de tórax se mostraram alteradas em 92% dos casos. Demonstrou-se associação da infecção por C. trachomatis com duração de internação superior a 15 dias (p = 0,0398) e com oxigenoterapia (p = 0,0484). CONCLUSÕES: Houve alta prevalência de ITRI por C. trachomatis na população estudada. A infecção por esta bactéria foi associada a uma forma mais grave da doença, demonstrando a importância de se investigar essa infecção na gestante de forma a evitar o adoecimento de recém-nascidos.

OBJECTIVES: To determine the prevalence of lower respiratory tract infection (LRTI) due to Chlamydia trachomatis in newborn infants and to describe the clinical, laboratory, and radiological characteristics of the disease. METHODS: A cross-sectional study carried out over a 12-month period. All infants up to 6 months of age admitted consecutively at the Centro Pediátrico Professor Hosannah de Oliveira of the Universidade Federal da Bahia in Salvador, Brazil, and diagnosed with LRTI according to clinical and/or radiological criteria were included in the study. C. trachomatis infection was diagnosed by the enzyme-linked immunosorbent assay (ELISA) for the detection of IgM-class antibodies. The prevalence of LRTI by C. trachomatis was determined and the prevalence ratios for the infection and clinical or laboratory variables were calculated. RESULTS: One hundred and fifty-one infants were submitted to serology for C. trachomatis and 15 (9.9%) tested positive. Chlamydial infection was found only in infants under 5 months of age, mainly in those aged under 2 months. Three of the infants with C. trachomatis infection were born by cesarean section. Conjunctivitis and eosinophilia had occurred in 33.3% of the cases. Chest X rays were abnormal in 92.0% of cases. There was an association between C. trachomatis infection and the duration of hospitalization exceeding 15 days (p = 0.0398) and oxygen therapy (p = 0.0484). CONCLUSIONS: There was a high prevalence of C. trachomatis respiratory infection in the population studied. The infection was associated with a more severe form of the disease, emphasizing the importance of testing pregnant women for this infection to avoid infection in the newborn infant.

Reduced posterior corpus callosum area in suicidal and non-suicidal patients with bipolar disorder.

BACKGROUND: Impulsivity is a characteristic of bipolar disorder (BD) that can contribute to the risk for suicidal behavior. Evidence suggests that gray and white matter abnormalities are linked with impulsivity, but little is known about the association between corpus callosum (CC) and impulsivity in BD. We examined the CC area and impulsivity in euthymic bipolar I patients, with and without lifetime history of suicide attempts, and in healthy controls. METHODS: Nineteen bipolar patients with a suicide attempt history (BP-S), 21 bipolar patients without suicide attempt history (BP-NS), and 22 healthy controls (HC) underwent clinical assessment by the Structured Clinical Interview with the DSM-IV axis I (SCID-I), the Barratt Impulsiveness Scale (BIS-11), and MRI scan. RESULTS: No differences were observed for any CC subregion between BP-S and BP-NS groups. There was a significant reduction in the genu (p=0.04) and isthmus areas (p=0.01), in bipolar patients compared with HC. In the BP-S group, the BIS-11 total (p=0.01), attention (p=0.001) and non-planning (p=0.02) impulsivity scores were significantly higher than in the BP-NS and HC groups. LIMITATIONS: These results cannot establish causality because of the cross-sectional nature of the study. CONCLUSION: This report potentially provides evidence that a reduction in the CC area is present even in non-symptomatic bipolar patients, which may be evidence of a biological trait marker for BD. Furthermore, the study demonstrated that BP-S group had higher impulsivity even during euthymia, which points to a sustained association between lifetime history of suicide attempts and impulsivity in BD.

Seasonal patterns of viral and bacterial infections among children hospitalized with community-acquired pneumonia in a tropical region.

Community-acquired pneumonia (CAP) is a common cause of morbidity among children. Evidence on seasonality, especially on the frequency of viral and bacterial causative agents is scarce; such information may be useful in an era of changing climate conditions worldwide. To analyze the frequency of distinct infections, meteorological indicators and seasons in children hospitalized for CAP in Salvador, Brazil, nasopharyngeal aspirate and blood were collected from 184 patients aged < 5 y over a 21-month period. Fourteen microbes were investigated and 144 (78%) cases had the aetiology established. Significant differences were found in air temperature between spring and summer (p = 0.02) or winter (p < 0.001), summer and fall (p = 0.007) or winter (p < 0.001), fall and winter (p = 0.002), and on precipitation between spring and fall (p = 0.01). Correlations were found between: overall viral infections and relative humidity (p = 0.006; r = 0.6) or precipitation (p = 0.03; r = 0.5), parainfluenza and precipitation (p = 0.02; r = -0.5), respiratory syncytial virus (RSV) and air temperature (p = 0.048; r = -0.4) or precipitation (p = 0.045; r = 0.4), adenovirus and precipitation (p = 0.02; r = 0.5), pneumococcus and air temperature (p = 0.04; r = -0.4), and Chlamydia trachomatis and relative humidity (p = 0.02; r = -0.5). The frequency of parainfluenza infection was highest during spring (32.1%; p = 0.005) and that of RSV infection was highest in the fall (36.4%; p < 0.001). Correlations at regular strength were found between several microbes and meteorological indicators. Parainfluenza and RSV presented marked seasonal patterns.

Procalcitonin is useful in identifying bacteraemia among children with pneumonia.

Empirical antibiotic use is prescribed in managing children with pneumonia worldwide. We assessed the usefulness of procalcitonin (PCT) and interferon-alpha (IFN-alpha) in differentiating viral from bacterial pneumonia. Among 159 hospitalized children, pneumonia was diagnosed based on clinical complaints plus pulmonary infiltrate. Aetiology was investigated for 9 viruses and 4 atypical and 3 typical bacteria. PCT and IFN-alpha were measured in the serum sample collected on admission. Eight patients had bacteraemic infections, 38 had non-bacteraemic typical infections, and 19 patients had atypical bacterial infections. Viral and unknown aetiology was established in 57 (36%) and 34 (21%) cases, respectively. Three patients with bacterial infection without collected blood culture were excluded. IFN-alpha (IU/ml) was detectable in 20 (13%) cases. The difference among median PCT values of the bacteraemic (4.22; 1.56-7.56), non-bacteraemic typical bacterial (1.47; 0.24-4.07), atypical bacterial (0.18; 0.06-1.03) and only viral (0.65; 0.11-2.22) subgroups was significant (p = 0.02). PCT was > or =2 ng/ml in 52 (33%) cases. The presence of IFN-alpha was associated with PCT <2 ng/ml (90% vs. 64%, p = 0.02). The negative predictive value (95% confidence interval) of PCT > or =2 ng/ml was 95% (89-100%), 89% (78-100%), 93% (85-100%) for differentiation of bacteraemic from viral, atypical bacterial and non-bacteraemic typical bacterial infection, respectively, and 58% (49-68%) for differentiation between bacterial and viral infection. PCT may be useful in identifying bacteraemia among children hospitalized with community-acquired pneumonia. IFN-alpha was uncommonly detected.

Clinical failure among children with nonsevere community-acquired pneumonia treated with amoxicillin.

OBJECTIVE: To estimate the clinical failure and adverse events in children with nonsevere pneumonia receiving amoxicillin, identifying risk factors. RESEARCH DESIGN/METHODS: 192 patients aged 2 - 59 months were prospectively followed up. Pneumonia diagnosis was based on respiratory complaints and radiographic pulmonary infiltrate or pleural effusion. Amoxicillin (50 mg/kg/day) was given. Demographic data and clinical findings on admission, daily evolution up to the 5th day of treatment and 2 - 4 weeks after enrollment were collected. MAIN OUTCOME MEASURES: Clinical failure included persistence of fever, difficulty breathing or tachypnea beyond the first 48 h of treatment or of cough beyond the first 96 h of treatment or sign of severe/very severe disease up to the 5th day of treatment. RESULTS: Amoxicillin failed in 6 (3.1%) cases. By excluding one child diagnosed with cystic fibrosis after continued follow-up, the final clinical failure rate was 2.6%. The total adverse effect frequency was 14 (7.3%), but amoxicillin was discontinued only in 1 (0.5%) case. No relapse was identified at the 2 - 4-week interval evaluation. By multivariate analysis, age (OR = 1.1; 95% CI 1.01 - 1.19) was an independent risk factor for clinical failure which occurred in older children (47 +/- 9 vs 31 +/- 16 months; p = 0.01). CONCLUSIONS: Clinical failures were few, especially among those aged < 2 years. Amoxicillin discontinuation due to adverse reaction was rare.

Human bocavirus in very young infants hospitalized with acute respiratory infection in northeast Brazil.

A cross-sectional study was carried out over a period of 12 months to investigate the occurrence of human bocavirus (HBoV) infection in infants hospitalized for respiratory infections in a teaching hospital in Salvador, Brazil, and to describe the clinical manifestations of this infection. Nasopharyngeal aspirates were collected from the children and immunofluorescence and polymerase chain reaction were performed to investigate the presence of respiratory viruses. HBoV was detected in 4 out of 66 patients. Two of the HBoV-positive infants were co-infected with other viruses. The principal clinical findings in HBoV-positive children were: nasal obstruction, catarrh, cough, fever and dyspnea. This study revealed HBoV infection in children aged <2 months, suggesting that the infection may occur at a very early age.

Pulmonary hemorrhage syndrome associated with dengue fever, high-resolution computed tomography findings: a case report.

Dengue hemorrhagic fever is an acute infectious disease caused by dengue virus. We described the high-resolution CT findings in a 70-year-old male with the disease, which was diagnosed by clinical examination and confirmed by serological methods. High-resolution CT demonstrated bilateral areas of consolidation with air bronchogram and ground glass opacities, as well as small bilateral pleural effusions. Dengue hemorrhagic fever should be considered in the differential diagnosis of diffuse pulmonary hemorrhage.

The role of respiratory viral infections among children hospitalized for community-acquired pneumonia in a developing country.

We report an investigation for 16 bacteria and viruses among 184 children hospitalized with pneumonia in Salvador, Brazil. Etiology was established in 144 (78%) cases. Viral, bacterial, and mixed infections were found in 110 (60%), 77 (42%), and 52 (28%) patients, respectively. Rhinovirus (21%) and Streptococcus pneumoniae (21%) were the most common pathogens. Our results demonstrate the importance of viral and pneumococcal infections among those patients.