Search

Children as a population have high antimicrobial prescribing rates which may lead to high resistance of bacteria according to data from some single-center surveys of antibiotic prescribing rates in China. The acquirement of baseline data of antibiotic prescribing is the basis of developing intervention strategies on inappropriate antimicrobial prescriptions. Few studies show clearly the pattern and detailed information on classes of antibiotics and distribution of indications of antibiotic prescriptions in children in China. This study aims to assess the antibiotic prescribing patterns among children and neonates hospitalized in 18 hospitals in China. A 24-hour point prevalence survey on antimicrobial prescribing was conducted in hospitalized neonates and children in China from December 1st, 2016 to February 28th, 2017. Information on the antibiotic use of patients under 18 years of age who were administered one or more on-going antibiotics in the selected wards over a 24-hour period was collected. These data were submitted to the GARPEC (Global Antimicrobial Resistance, Prescribing and Efficacy in Children and Neonates) web-based application ( https://pidrg-database.sgul.ac.uk/redcap/ ). For statistical analysis, Microsoft Excel 2007 and SPSS 22.0 were used. The antibiotic data were collected in 35 wards in 18 hospitals from 9 provinces. In total, 67.76% (975/1439) of the patients (n = 1439) were given at least one antibiotic, including 58.1% (173/298) of neonates (n = 298) and 70.3% (802/1141) of children (n = 1141). In neonates, the three most frequently prescribed antibiotics were third-generation cephalosporins (41.7%), penicillins plus enzyme inhibitor (23.8%), and carbapenems (11.2%). In children, the three most frequently prescribed antibiotics were third-generation cephalosporins (35.5%), macrolides (23.2%), and penicillins plus enzyme inhibitors (15.9%). The most common indication for antibiotics was proven or probable bacterial lower respiratory tract infection (30.9% in neonates and 66.6% in children). Antibiotics are commonly prescribed in the Chinese children population. It is likely that the third-generation cephalosporins and macrolides are currently overused in Chinese children. Efforts must be made to ensure safe and appropriate antibiotic prescribing to reduce and prevent the future development of antibiotic resistance.

BackgroundThe imbalanced respiratory microbiota observed in pneumonia causes high morbidity and mortality in childhood. Respiratory metagenomic analysis demands a comprehensive microbial gene catalogue, which will significantly advance our understanding of host–microorganism interactions.ResultsWe collected 334 respiratory microbial samples from 171 healthy children and 76 children with pneumonia. The respiratory microbial gene catalogue we established comprised 2.25 million non-redundant microbial genes, covering 90.52% of prevalent genes. The major oropharyngeal microbial species found in healthy children were Prevotella and Streptococcus. In children with Mycoplasma pneumoniae pneumonia (MPP), oropharyngeal microbial diversity and associated gene numbers decreased compared with those of healthy children. The concurrence network of oropharyngeal microorganisms in patients predominantly featured Staphylococcus spp. and M. pneumoniae. Functional orthologues, which are associated with the metabolism of various lipids, membrane transport, and signal transduction, accumulated in the oropharyngeal microbiome of children with pneumonia. Several antibiotic resistance genes and virulence factor genes were identified in the genomes of M. pneumoniae and 13 other microorganisms reconstructed via metagenomic data. Although the common macrolide/β-lactam resistance genes were not identified in the assembled M. pneumoniae genome, a single-nucleotide polymorphism (A2063G) related to macrolide resistance was identified in a 23S ribosomal RNA gene.ConclusionsThe results of this study will facilitate exploration of unknown microbial components and host–microorganism interactions in studies of the respiratory microbiome. They will also yield further insights into the microbial aetiology of MPP.

Background The diagnosis of pertussis in clinical practice continues to be a challenge worldwide as the symptoms are variable. We aimed to determine the prevalence of pertussis in Chinese children irrespective of cough duration and explore the clinical characteristics of children with pertussis with different cough durations. Methods This was a prospective study of children 1 month to 11 years of age with different cough durations in one large Chinese hospital. Bilateral deep posterior nasopharyngeal swabs and venepuncture for full blood count, CRP and serology and sputum were obtained when possible for investigation. E-test strips were used for testing the susceptibility of the B.pertussis isolates against erythromycin, azithromycin, sulphamethoxazole/trimethoprim, levofloxacin, amoxicillin and doxycycline. Demographic, clinical and laboratory information on culture and antimicrobial susceptibility testing was collected from children, and analyzed using SAS v.10 (SAS Institute Inc., USA). Results After exclusions we analyzed 312 children. Ninety-seven (31.1%) children had laboratory evidence of pertussis. When grouped by cough duration, few characteristics were significant between children with and without pertussis. Of the 36 isolates, 72.2% (26/36)could not be inhibited by erythromycin and azithromycin at all. The MIC50 and MIC90 to amoxicillin were 0.75 mg/L and 1 mg/L respectively, sensitive to amoxicillin by the EUCAST points. Conclusions The “one-size-fits-all” clinical pertussis case definition is no longer optimal to recognize this disease. A large comprehensive study of children with all types of cough is required to make substantial inroads into increasing both the sensitivity and specificity in pertussis diagnosis, which will have a beneficial impact on public health. Amoxicillin maybe an alternative for children with marolide-resistant B.pertussis infection; however, local sensitivities are required to inform clinical practice.

To describe the frequency and impact of bacterial co-infections in children hospitalized with Mycoplasma pneumoniae pneumonia.Retrospective, descriptive study.Tertiary-care hospital in Beijing, China.8612 children admitted to Beijing Childrens Hospital from June 2006 to June 2014.According to the testing results of etiology we divided the cases into pure M. pneumoniae infection group and mixed bacterial infection group. We analyzed clinical features, hospital expenses and differences between these two groups.173 (2%) of included children had bacterial coinfection. 56.2% of bacterial pathogens were identified as Streptococcus pneumoniae.The most common bacterium causing co-infection in children with M. pneumoniae pneumonia was S. pneumoniae.

Background Streptococcus pneumoniae 7-valent conjugate vaccine (PCV7) was made available in China in the private sector in September 2008. Methods This study investigated the serotype distribution, antibiotic resistance, and molecular characteristics of S. pneumoniae in hospitalized pediatric patients. Pneumococcal isolates were collected from hospitalized children younger than 14 years. Their serotypes were determined using Quellung reactions with antisera; antibiotic resistance against 13 antimicrobials was tested using the E-test method or disc diffusion. The sequence types (STs) were analyzed with multilocus sequence typing. Results A total of 187 pneumococcal specimens were collected, including 21 invasive and 166 noninvasive isolates. The prevailing serotypes were 19F (31.6%), 19A (19.8%), 23F (11.2%), 6A (9.1%), 14 (9.1%) and 15B (5.9%). The coverage rates of PCV7, PCV10 and PCV13 were 56.2% (105/187), 56.7% (106/187) and 86.1% (161/187), respectively. The overall nonsusceptibility rate against penicillin was 8.0%; however, this rate would have been 91.5% if based on an oral breakpoint. All but one of the isolates were highly resistant to erythromycin. Multidrug resistance was exhibited by 177 (94.7%) isolates. The 5 predominant multilocus sequence typings for all pneumococci were ST271 (24.1%), ST320 (18.2%), ST81 (7.5%), ST876 (7%) and ST3397 (5.3%), which were primarily related to serotypes 19F, 19A, 23F, 14 and 15B, respectively. CC271 was the most frequent antibiotic-resistant complex clone. Conclusions The coverage rates of PCVs were high, and the antibiotic resistance rates were of serious concern among hospitalized children. Universal immunization using PCVs would likely prevent episodes of S. pneumoniae diseases and the spread of antibiotic resistance in Beijing.

Background Community-acquired pneumonia in children is common in China. To understand current clinical characteristics and practice, we conducted a cross-sectional study to analyze quality of care on childhood pneumonia in eight eastern cities in China. Methods Consecutive hospital records between January 1, 2010 and December 31, 2010 were collected from 13 traditional Chinese medicine (TCM) and western medicine (WM) hospitals in February, May, August, and November (25 cases per season, 100 cases over the year), respectively. A predesigned case report form was used to extract data from the hospital medical records. Results A total of 1298 cases were collected and analyzed. Symptoms and signs upon admission at TCM and WM hospitals were cough (99.3% vs. 98.6%), rales (84.8% vs. 75.0%), phlegm (83.3% vs. 49.1%), and fever (74.9% vs. 84.0%) in frequency. Patients admitted to WM hospitals had symptoms and signs for a longer period prior to admission than patients admitted to TCM hospitals. Testing to identify etiologic agents was performed in 1140 cases (88.4%). Intravenous antibiotics were administered in 99.3% (595/598) of cases in TCM hospitals and in 98.6% (699/700) of cases in WM hospitals. Besides, Chinese herbal extract injection was used more frequently in TCM hospitals (491 cases, 82.1%) than in WM hospitals (212 cases, 30.3%) (p < 0.01). At discharge, 818 cases (63.0%) were clinically cured, with a significant difference between the cure rates in TCM (87.6%) and WM hospitals (42.0%) (OR = 9.8, 95% confidence interval (CI): 7.3 ~ 12.9, p < 0.01). Pathogen and previous medical history were more likely associated with the disappearance of rales (OR = 7.2, 95% CI: 4.8 ~ 10.9). Adverse effects were not reported from the medical records. Conclusions Intravenous use of antibiotics is highly prevalent in children with community-acquired pneumonia regardless of aetiology. There was difference between TCM and WM hospitals with regard to symptom profile and the use of antibiotics. Intravenous use of herbal injection was higher in TCM hospitals than in WM hospitals. Most of the cases were diagnosed based on clinical signs and symptoms without sufficient confirmation of aetiology. Audit of current practice is urgently needed to improve care.

Acute respiratory tract infections (ARI) are the leading cause of pediatric morbidity and mortality worldwide, particularly in developing countries. Viruses are the main pathogens of ARI in children. The purpose of the present study was to determine the epidemiologic features of respiratory viruses, including novel viruses, in outpatient and hospitalized children with ARI.From March 2010 to February 2012, 2066 children with ARI, including 1050 outpatients and 1016 inpatients, were involved in this study. One nasopharyngeal aspirate or throat swab specimen was collected from each patient. Reverse transcription (RT) PCRs were performed to detect common respiratory tract viruses including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV) type 1-4, adenovirus (ADV), enterovirus (EV), human coronavirus (HCOV), human metapneumonia virus (HMPV) and human bocavirus (HBOV).At least one viral pathogen was identified in each of 1274 out of 2066 patients and the overall positive rate was 61.7%. The positive rate in inpatient (69.7%) was higher than that in outpatient (53.9%). The frequencies of detection of various viruses among in- and outpatients were different. RSV was the most prevalent virus detected among hospitalized children, followed by HRV and PIV, whereas IFV was the most frequently identified virus in the outpatient group, followed by ADV and PIV. Simultaneous detection of two or more viruses was found in 377 cases. Coinfection was more frequent in inpatients than in outpatients (30.1% vs. 6.8%, P0.001).Respiratory viruses play an important role in children with ARI, especially in young children. RSV was the most prevalent virus detected among hospitalized children, whereas IFV was the most frequently identified virus in the outpatient group. Viral coinfections are frequently identified, particularly in hospitalized patients. Further studies are required to better understand the impact of coinfections in children with ARI.

Objective. To understand the viral etiology of acute childhood encephalitis in Beijing. Methods. Ninety-seven Chinese children (between 7 months and 13 years of age) with acute encephalitis were retrospectively investigated. They were treated in Beijing Children's Hospital between June, 1991, and October, 1994. Different serologic methods (immunofluorescence assay, enzyme-linked immunosorbent assay, solid phase reverse immunosorbent test) were used for detection of IgM antibody to enteroviruses, herpesviruses, mumps, measles, rubella and Japanese encephalitis virus. The viral DNA of six herpesviruses was detected by polymerase chain reaction. Results. Viral etiology was identified in 35 of 97 (36.0%) cases. The most frequently identified pathogens were enteroviruses (15 ; 15.4%), followed by mumps (7 ; 7.2%), rubella (6 ; 6.1%), Japanese encephalitis virus (5 ; 5.1%), human herpesvirus 6 (2 ; 2.0%), herpes simplex virus (2 ; 2.0%) and Epstein-Barr virus (1 ; 1.0%). IgM antibody in cerebrospinal fluid was detected for enterovirus, mumps and rubella viruses. Conclusions. Enteroviruses were the most frequent viral pathogens of acute childhood encephalitis in Beijing. Detection of IgM in cerebrospinal fluid may be useful for diagnosis in certain cases of viral encephalitis.

To summarize clinical and molecular features of two children with autosomal recessive chronic granulomatous disease caused by CYBA mutations.The clinical records and CYBA mutations were reviewed for analysis of infections and inflammatory complications.The first case was a girl diagnosed with "liver and spleen abscess" in our hospital when she was 2.9 years old, with past history of neonatal impetigo and recurrent purulent lymphadenitis and positive family history. The results of DHR123 flow-cytometry showed that positive phagocytes after phorbol ester (PMA) stimulation was 84.63%. CYBA mutation analysis showed that she had heterozygous 35CT, Q3X and IVS-2AG. The second case was a boy diagnosed with "sepsis (salmonella D)" when he was 4 years old with a past history of impetigo, sepsis, perianal abscess, skin infection and positive family history. The results of flow cytometry showed that positive phagocytes after PMA stimulation was 96.13%. CYBA mutation analysis showed that he had homozygous 35CT, Q3X and his parents were all carriers. All of them had BCG related axillary lymphnode calcification.A22CGD cases had recurrent purulent infections (skin, lymphnode, liver and spleen, lung, blood), DHR123 flow cytometric analysis helped the diagnosis of CGD, CYBA mutation analysis ascertained the diagnosis of A22CGD.

In recent years, the incidence of allergic diseases in China is increasing. With serious influence on the patients' quality of life and even life-threatening, now allergic diseases have become an important public health problem in our country. This survey aimed to obtain a general epidemic outline of children's major allergic diseases, i.e., childhood asthma, allergic rhinitis and eczema in the downtown of Beijing, Chongqing and Guangzhou.Childhood asthma questionnaire was established by Delphi method based on guidelines for childhood asthma diagnosis and prevention made by Chinese medical association in 2008 with reference to the International Study of Asthma and Allergies in Childhood questionnaire (ISAAC). This study was carried out from Oct. 2008-Mar. 2009, in Beijing, Chongqing and Guangzhou by a multi-stage sampling method, covering a sample of 24 290 children aged 0 - 14 years by a multi-stage sampling method, the population of children surveyed in the downtown of Beijing Chongqing and Guangzhou was 10 372, 9874 and 4072 respectively; of whom males were 5545, 5258, 2159, and females were 4917, 4588, 1877; the ratio of males to females in the three cities were 1.11:1, 1.15:1, 1.15:1; the average age of surveyed children were 7.63, 8.74 and 8.30 years old. All the questionnaire was filled in by the parents of children or other guardian of children.The self-reported prevalence of asthma in Beijing, Chongqing and Guangzhou was 3.15%, 7.45%, 2.09%, the self-reported prevalence of allergic rhinitis was 14.46%, 20.42%, 7.83%, and the prevalence of eczema was 20.64%, 10.02%, 7.22%. In the survey, asthma combined with allergic rhinitis had the highest rate, 49.54%, 50.14%, 34.83%, respectively in the 3 cities. The self-reported prevalence of asthma and allergic rhinitis was significantly higher in male than female. Besides, the self-reported prevalences of asthma and allergic rhinitis were relatively lower in children under 1 year and over 10 years of age.The prevalence of asthma, allergic rhinitis and eczema and other allergic diseases in children 0 - 14 years of age in the three cities gradually increased, and the prevalence of allergic diseases in Chongqing was relatively higher.

Viruses are common pathogens of acute lower respiratory tract infection (ALRTI) in children. There are few studies on consecutive monitoring of viral pathogens of ALRTI in a larger cohort during the past several years. The aim of this study was to investigate the viral pathogens of ALRTI in children of different age groups and to outline the epidemic feature of different viruses.(1) Totally 1914 (1281 male and 709 female) children with clinical diagnosis of ALRTI during the period of March 2007 to March 2010 were recruited into this study. These patients were hospitalized patients in department of internal medicine or outpatients in emergency department in Beijing Children's Hospital. The patients were divided into four groups, including 1072 patients1 year old, 326 patients 1-3 years old, 158 patients 3-6 years old, 358 patients ≥ 6 years old. One nasopharyngeal aspirate specimen was collected from each patient. Reverse transcription (RT) PCR methods were applied to detect common respiratory viruses including respiratory syncytial virus (RSV), human rhinovirus (HRV), influenza virus type A, B and C (IFA, IFB, IFC), parainfluenza virus (PIV) type 1-4, adenovirus (ADV), enterovirus (EV), human coronavirus (HCOV), human metapneumovirus (HMPV) and human bocavirus (HBOV).(1) The total positive rate of viruses was 70.3%. The positive rate was 83.0% (890/1072) in the group of1 year old, and 80.1% (261/326) in group of 1-3 years old, 60.8% (96/158) in group of 3-6 years old and 27.7% (99/358) in group of ≥ 6 years old, respectively. There was a significant difference in the positive rate among different age groups (χ² = 2213.5, P = 0.000). The top three viruses were RSV, HRV and PIV; and the positive rates were 50.9%, 36.2% and 12.0% respectively in group of1 year old. (2) The epidemic seasons of RSV and HRV were winter and spring, and PIV infection was epidemic in spring and summer. (3) The detection rates of 2 or more viruses were 38.2%, 36.4%, 30.2% and 15.2% in groups of1 year old, 1-3 years old, 3-6 years old and ≥ 6 years old, respectively. There was a significant difference in the mixed infection rate among different age groups (χ² = 1346.00, P = 0.000).RSV, HRV and PIV were the most predominant pathogens in younger children with ALRTI. Different viral infections had different seasonal features. Mixed infections with two or more viruses were detected in substantial proportion of patients with ALRTI, but further studies are needed to explore the clinical significance of mixed infection with viruses in patients with ALRTI.

To study the effects of specific immunotherapy with standardized house dust mite extract on the lung function and immunologic markers in children with asthma.Thirty-two children with mild to moderate asthma who were allergic to house dust mite were assigned to two groups: an immunotherapy group that received subcutaneous specific immunotherapy with standardized house dust mite extract beside glucocorticoids treatment (n=15) and a control group that received glucocorticoids treatment alone (n=17). Lung function was determined before treatment and 3, 6, 12, 18 and 24 months after treatment. The frequency of asthma attacks was observed before treatment and 12 and 24 months after treatment. Serum immunological markers, including total IgE, specific IgE and specific IgG4 against house dust mite (Dermatophagoides pteronyssinus, Der P), ECP, IL-10, IL-4, and IFN-γ, were measured before treatment and 12 and 24 months after treatment.The parameters of lung function were kept at the normal level or near normal level after treatment in the immunotherapy group. Compared with before treatment, the percentage of patients without asthma attacks increased significantly after treatment in the immunotherapy group (P0.05) and increased more significantly with a prolonged treatment time (P0.05). The level of serum sIgG4 against Der P increased significantly throughout the period of the immunotherapy treatment compared with before treatment (P0.01). There were no significant differences in the levels of serum total IgE, sIgE against Der P, ECP, IL-10, IL-4 and IFN-γ before and after treatment in the immunotherapy group. There were no significant differences in all the parameters measured before and after treatment in the control group.Subcutaneous specific immunotherapy with standardized house dust mite extract for two years decreases the frequency of asthma attacks and the lung functions are kept in a normal level in children with asthma. The role of the specific immunotherapy may attribute to the increased level of serum sIgG4 against Der P.

The clinical characteristics of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) are largely unreported in the pediatric patients in mainland of China. The main aim of this study was to recognize the clinical features of EBV-HLH in children and to explore its prognosis and risk factors.A retrospective study was performed on 78 pediatric patients with EBV-HLH who were admitted to Beijing Children's Hospital between 2003 and 2008. All patients' medical records were reviewed and analyzed. For each patient, demographic, clinical, laboratory and outcome information was collected. Statistical analysis was conducted via multivariate and univariate analysis.The age of onset peaked between 1 - 2 years and boys were more likely developed EBV-HLH. EBV-HLH occurred mainly in the serological pattern with EBV nuclear antigen (EBNA) positive (70.5%). The overall fatality of the disease was 56.7%. Twelve of the 39 fatalities (30.8%) died rapidly within 2 months after diagnosis. Multivariate analysis revealed that not receiving chemotherapy (P = 0.002),or = 4 weeks of illness prior to diagnosis (P = 0.004), and albumin levels20 g/L (P = 0.045) significantly predicted an increased fatality risk.EBV-HLH is a severe disease with a high fatality rate that occurs mainly in the serological pattern with EBNA positive. Early initiation of chemotherapy and timely diagnosis significantly improves survival rate. Practical strategies should focus on reducing the likelihood of early death.

Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response. Interleukin-10 (IL-10) plays a crucial role in inducing allergen-specific tolerance. However the reports of the changes of IL-10 in house dust mite (HDM)-specific immunotherapy were varied. The aim of this study was to evaluate the function of IL-10-secreting regulatory T cells in asthma children successfully treated with HDM immunotherapy.Peripheral blood mononuclear cells (PBMCs) were isolated from 27 patients following 1.5 - 2 years of HDM-specific immunotherapy (SIT, SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthma group). After 48 hours of in vitro stimulation with HDM extracts, IL-10-secreting regulatory T cells were measured by four colour flow cytometry. Sera were tested for allergen-specific IgG(4) and IgE using the Immuno CAP 100 assay.PBMCs from children undergoing immunotherapy following HDM extracts stimuli produced significantly more IL-10 compared with the asthma group. The frequency of iTreg cells and aTreg cells increased in SIT group after HDM stimulation, while it was not affected in the asthma group. Among the iTreg cells and aTreg cells, the frequency of CD4(+)CD25(-)Foxp3(-)IL-10(+) Treg cells increased the most which was 2 times higher than that in unstimulated cultures in SIT group. The levels of HDM-specific IgG(4) of SIT group was significiently higher compared with asthma group, but there was no correlation of the levels of HDM-specific IgG(4) and IL-10 secreting Treg cells.HDM-specific immunotherapy can successfully upregulate the frequency of IL-10-secreting Treg cells. CD4(+)CD25(-)Foxp3(-)IL-10(+) Treg cells may play a key role in inducing the immune tolerance in HDM-specific immunotherapy.

To identify the clinical characteristics of and to explore the prognostic factors influencing mortality in children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH).A retrospective study was conducted on 62 pediatric patients with EBV-HLH who were admitted to our hospital between 2003 and 2008. All their medical records were reviewed and analyzed. For each patient, demographic, clinical and laboratory data, genetic findings and outcome information were collected. The patients were divided into two groups: deceased or survived based on the follow-up results. Comparative analysis of the data was done by using independent-samples t test and Logistic multiple and univariate regression.(1) Among the 62 EBV-HLH patients, 36 were male and 26 were female. The age of onset ranged from 2 months to 14 years and most of the patients were between 1 and 3 years of age. EBV-HLH occurred mainly in the setting of reactivation (61.3%). (2) All patients exhibited persistent or intermittent fever and cytopenia/= 2 cell lines. Most of the patients presented with hepatomegaly (83.9%), splenomegaly (72.6%) and lymphadenopathy (69.4%). The main laboratory features showed an elevation of serum ferritin and aminotransferase levels. A reduction in serum albumin was observed and exhibited coagulopathy with hypofibrinogenemia and hypertriglyceridemia in most of the patients. Forty-eight of patients had hemophagocytosis in bone marrow at diagnosis of EBV-HLH. The serum EBV DNA level in 14 of 31 patients with EBV-HLH was in the range of 5.12 x 10(2) - 7.69 x 10(7) copies/ml with a mean value of 10(3.9) copies/ml. (3) Three heterozygous mutations in coding region were found, which resulted in amino acid change (C102F, S108N and T450M) in 3 patients. One patient had compound heterozygous mutations (S108N and T450M) in the PRF1 gene as the background defect and documented familial HLH type 2 (FHL2). (4) During the observational period, 35 of 57 patients (61.4%) died 3 months to 3 years after the onset, while 21 of whom died despite aggressive polychemotherapy, 15 of whom died within 2 months after hospitalization. The deceased patients were more likely to have lower albumin level and more prolonged activated partial thromboplastin time than the survived patients (P0.05 for all comparisons). Multivariate Logistic regression analysis revealed that duration of illness/= 1 month, non-chemotherapy, albumin level/ = 25 microg/L and internal organs hemorrhage were related with the prognosis significantly (P0.05 for all comparisons).This study revealed that EBV-HLH infection in pediatric patients had severe clinical courses and prognosis was poor and the majority of cases underwent EBV reactivation. The early diagnosis, prompt and proper chemotherapy can improve the survival rate. The duration of illness/= 1 month, non-chemotherapy, decreases in albumin and internal organs hemorrhage were the risk factors related to mortality in children with EBV-HLH.

To study the clinical features and diagnostic methods of mycoplasma pneumonia complicated with cerebral infarction.Data of 3 children with mycoplasma pneumonia who developed cerebral infarction, including clinical manifestations and imaging were collected, analyzed and the literature was reviewed.All the cases were pre-school or school-aged children, who developed the respiratory infection initially, the neurological symptoms were acute hemiparesis, with or without convulsion. The IgM antibody to Mycoplasma pneumoniae (Mp) was positive. Pulmonary imaging showed unilateral consolidation with atelectasis and pleural exudate. Neuroimaging showed occlusion of middle cerebral artery and infarction of its territory. After giving azithromycin, anti-coagulative and thrombolytic treatments, the neurological deficits recovered to some extent.Mycoplasma pneumonia were diagnosed based on respiratory symptoms and pulmonary imaging, the accompanied cerebral infarction was confirmed by neurological and neuroimaging findings.

Recent studies have reported germline mutations in the perforin gene (PRF1) in some types of hemophagocytic lymphohistiocytosis (HLH). However, the prevalence of PRF1 mutations in HLH in Chinese pediatric patients has not been extensively studied. The aim of this study was to investigate the prevalence of mutations and sequence variations in the PRF1 gene in Chinese pediatric patients with HLH.Polymerase chain reaction (PCR) was performed with five pairs of primers for the coding exons and the flanking intron sequences of PRF1. Sequencing of PCR products was subsequently applied in 30 pediatric patients with HLH and in 50 controls.Three heterozygous mutations in a coding region were found, which resulted in amino acid changes (C102F, S108N and T450M) in three patients. These mutations were not detected in control subjects. One patient had compound heterozygous mutations (S108N and T450M) in PRF1 as the background defect, and documented familial HLH type 2 (FHL2). One synonymous sequence variant (Q540Q) was observed in one patient but not in the controls. Two SNPs (A274A, H300H) in the coding region were detected in HLH patients and controls, but without differences in the heterozygosity rate between the two groups (P0.05 for all comparisons).We have identified three patients with three heterozygous missense mutations in PRF1; two of those three mutations (C102F and S108N) have so far been found only from Chinese patients. These findings are useful in evaluating the prevalence of PRF1 mutations in Chinese pediatric patients with HLH, and to correlate their genotype with phenotype. Some patients without familial history probably have primary HLH, which should be suspected even beyond the usual age range.

Chronic active Epstein-Barr virus infection (CAEBV) has been previously reported to be sometimes associated with an aggressive clinical course. The characteristics of CAEBV in Mainland Chinese pediatric patients are largely unreported. The main aims of this survey were to recognize the clinical features of CAEBV in children and to explore its diagnostic criteria and risk factors.A retrospective study was performed on 53 pediatric patients (36 boys and 17 girls) with CAEBV who were admitted to Beijing Children's Hospital between 2003 and 2007. All their medical records were reviewed and analyzed. For each patient, demographic, clinical, laboratory data and outcome were collected. Independent-samples t test was used for statistical analysis.The age at onset of CAEBV was from 2 months to 14.6 years (mean (5.3+/-3.3) years). At the time of onset, 43.4% patients had an infectious mononucleosis-like symptom. Most patients exhibited intermittent fever (92.5%, 49/53), hepatomegaly (81.1%, 43/53) and splenomegaly (77.4%, 41/53). Life-threatening complications including hemophagocytic syndrome (24.5%, 13/53), interstitial pneumonia (24.5%, 13/53), hepatic failure (15.1%, 8/53) and malignant lymphoma (11.3%, 6/53) were also observed. The serum EBV DNA level in 23 patients with CAEBV was in the range of 5.05 x 10(2)-4.60 x 10(6) copies/ml with a mean value of 10(3.7) copies/ml. Many patients with CAEBV generally had continuous symptoms during the observational period. Eleven out of 42 patients (26.2%) died 7 months to 3 years after onset. Deceased patients were more likely to have had lower platelet counts and albumin levels than the living patients (P0.05 for all comparisons).The study reveals that CAEBV in Chinese pediatric patients has a severe clinical course and prognosis is poor. Thrombocytopenia and decreases in albumin might potentially be risk factors for a poor prognosis. EBV loads should be measured and tissue should be stained on hybridization probes for EBV-encoded small RNA (EBER) if a patient presents with the known symptoms of CAEBV.

Although primary ciliary dyskinesia (PCD) is a group of inherited diseases, accurate diagnosis and appropriate clinical care to prevent and treat the complications could maintain patients' quality of life and normal life span. The diagnosis of PCD may often be delayed because it is frequently misdiagnosed as bronchitis, sinusitis and otitis. This study aimed to analyze and summarize the clinical features of PCD and explore diagnostic and differential diagnostic procedures in children.Patients were all chosen from the inpatient department of Beijing Children's Hospital, Capital Medical University between 1990 - 2006. The tunica mucosa bronchiorum and/or nasal mucous membrane were gained through bronchoscope in children suspected to have PCD. The ciliary ultrastructures were analyzed through the electron microscope. The clinical features and procedures of the diagnosis and differential diagnosis in children with PCD were analyzed.There were totally 26 children diagnosed as PCD with 10 (38.5%) Kartagener syndrome. All Kartagener syndrome children had mirror image dextrocardia with normal cardiac structure and situs inversus viscerum. The bronchoscopy performed in eight of 10 Kartagener syndrome children showed bronchus transposition. Twenty-six children came from twenty-five families. Although the siblings of four probands also had the symptoms of chronic cough with sputum, running nose and recurrent respiratory infections, only a boy and his sister were diagnosed as Kartagener syndrome simultaneously. Their parents and the other family members were healthy. Of the 26 patients, 11 were boys and 15 were girls. The median age at diagnosis was 8.7 years. The age of onset was between the second day after delivery and fifteen years old, median age was 3 years. The course of disease before diagnosis was eleven days to twelve years (median 3.5 years). All the children had the symptom of cough, 24 of which had productive cough. Seven cases were found to have clubbing fingers. Dynein arm defect was found in 10 children, 6 of them had total absence of dynein arms and 4 had decreased dynein arm numbers. Microtube derangements were found in 8 children. One Kartagener syndrome child had a normal cilia structure. Bronchiectasis, consolidation and increased lung markings were found in 8, 6 and 7 patients separately on the radiographic study. Twenty patients had sinusitis. Nine of sixteen children had decreased PEF, FEV1 and/or FEF 25 - 75 on the pulmonary function test. Fifteen culture samples obtained from 6 children's sputum and/or bronchoalveolar lavage fluid were positive for 8 strains of Pseudomonas aeruginosa, 5 strains of Streptococcus pneumoniae and 2 strains of Candida albicans. In 1 subject more than one organism were found in the same sample. Hearing lost and gastroesophageal reflux were detected in 3 of 4 and 3 of 5 examined children respectively.The onset of PCD can occur from neonate to adolescence and usually has a chronic course. The common symptom of pediatric PCD was productive cough and significant growth retardation. The most common ultrastructural abnormalities associated with PCD were the total absence of dynein arms, decreased dynein arm numbers and microtube derangement. Some patients have normal ciliary structures. Bronchiectasis, consolidation and sinusitis were usually seen on the radiography. Pseudomonas aeruginosa and Streptococcus pneumoniae were the two common bacterial organisms obtained from sputum and/or bronchoalveolar lavage fluid of PCD children. Some patients have mixed infections. PCD children have high percentages of hearing lost and gastroesophageal reflux.

Bronchiolitis obliterans (BO) is a chronic airflow obstruction syndrome associated with inflammatory lesions of the small airways. The etiology, pathogenesis, effective treatment and prognosis of this disorder remain uncertain by now. There has been no large scale clinical research on BO in China. This study aimed to analyze the clinical characteristics of BO in children.Clinical analysis was done on data of 42 patients (31 boys and 11 girls, aged from 7 months to 12 years and 2 months) with bronchiolitis obliterans diagnosed and treated in Beijing Children's Hospital from April 2001 to August 2007. The diagnostic criteria included typical clinical manifestations, specific pulmonary CT imaging and lung function tests.All the patients presented with persistent cough and wheezing. Crackles and wheezing were heard in most cases. Thirty-two (76.2%) cases were post-infectious BO, among whom 8 (25%) were supposed to be adenovirus pneumonia, 7 (21.9%) measles pneumonia and 2 (6.2%) respiratory syncytial virus infection. In 4 (9.5%) cases BO occurred after Steven-Johnson syndrome, and 1 (2.4%) after bone marrow transplantation. The constrictive obstruction in small airway occurred in 35 cases (89.7%), while mixed pattern in 4 (10.3%). Pulmonary CT revealed mosaic perfusion in 34 cases (81.0%), bronchiectasis in 14 cases (33.3%), bronchial wall thickening in 14 cases (33.3%), atelectasis in 4 cases (9.5%) and Swyer-James syndrome in 2 cases (4.8%). All the cases received oral corticosteroid and low doses of erythromycin or azithromycin, with corticosteroid and bronchodilator inhalation or oral montelukast. Follow up time was from 1 month to 5 years. Besides 2 cases in whom the disease was ameliorated in clinical presentation, pulmonary imaging and function, the rest experienced deterioration and one died.In most of the patients BO occurred following infections. The specific clinical presentations, imaging and pulmonary function are sufficiently informative for diagnosis. Most of the cases enrolled in this study had a poor outcome.

Human bocavirus (HBoV) is a parvovirus recently found to possibly cause respiratory tract disease in children and adults. This study investigated HBoV infection and its clinical characteristics in children younger than five years of age suffering from acute lower respiratory tract infection in Beijing Children's Hospital.Nasopharyngeal aspirates were collected from children suffering from acute lower respiratory tract infection during the winters of 2004 to 2006 (from November through the following February). HBoV was detected by polymerase chain reaction amplification and virus isolation and the amplification products were sequenced for identification.HBoV infection was detected in 16 of 333 study subjects. Coinfections with respiratory syncytial virus were detected in 3 of 16 HBoV positive patients with acute lower respiratory tract infection. The median age for HBoV positive children was 8 months (mean age, 17 months; range, 3 to 57 months). Among the HBoV positive children, 14 were younger than 3 years old, 9 were younger than 1 year old and 7 were younger than 6 months. These 16 positive HBoV children exhibited coughing and abnormal chest radiography findings and more than 60% of these children had wheezing and fever. Ten children were clinically diagnosed with pneumonia, 2 bronchiolitis, 2 acute bronchitis and 2 asthma. One child died.HBoV was detected in about 5% of children with acute lower respiratory infection seen in Beijing Children's Hospital. Further investigations regarding clinical and epidemiologic characteristics of HBoV infection are needed.

The objective of this study was to observe for any change in baseline seizure frequency with acupuncture in children with cerebral palsy.A randomized controlled study was conducted: Group I consisted of integrated acupuncture, tuina, and rehabilitation (physiotherapy, occupational therapy, and hydrotherapy) for 12 weeks; and Group II consisted of rehabilitation (physiotherapy, occupational therapy, and hydrotherapy) for 12 weeks. After a washout period of 4 weeks, Group II then received acupuncture and tuina for 12 weeks. Each subject received 5 daily acupuncture sessions per week for 12 weeks (total = 60 sessions). All children were assessed for any change in seizure frequency during treatment.One hundred and sixteen (116) children were recruited and randomized into Group I (N = 58) and Group II (N = 58). Thirty-three (33) children withdrew (9 from Group I and 24 from Group II). Of the remaining 83 children, Group I consisted of 49 and Group II of 34 children. For baseline, 5 children (6%; 5/83) had seizures. During phase 1 (12 weeks) of integrative treatment and subsequent 4-week follow-up, 3 children in Group I had seizures. Among those 3 children with seizures, 1 child with prior history of recurrent febrile seizure had 3 more recurrent febrile seizures during acupuncture treatment and 2 children without any prior history of seizures had new-onset seizures (1 with 3 recurrent febrile seizures and 1 with afebrile seizure). For Group I, 2 children with epilepsy had no increase in seizure frequency during acupuncture treatment. For Group II during the phase 2 acupuncture period, none had increase in seizure frequency. In both groups, 4 of 5 children (80%; 2 in Group I and 2 in Group II) with seizures had no increase in seizure frequency during acupuncture treatment and follow-up.The risk of increasing seizure is not increased with acupuncture treatment for cerebral palsy.

To investigate the correlation of Epstein-Barr virus (EBV) infection and childhood lymphoma.Paraffin-embedded specimens of lymphoma collected between 1996 and 2005, including 36 Hodgkin lymphomas (HL) and 51 non-Hodgkin lymphomas (NHL), were included in this study. Paraffin-embedded specimens of reactive hyperplasia of lymph nodes (RL) collected during the same period were used as controls. Immunohistochemical (IHC) assay was used to detect EBV-LMP1 and in situ hybridization (ISH) to detect EBV-EBERs.EBV was detected in 72.2% (26/36) of the Hodgkin lymphomas, 15.7% (8/51) of the non-Hodgkin lymphomas and 33.3% (15/45) of the reactive hyperplasia of lymph nodes. There was a significant difference among Hodgkin lymphoma, non-Hodgkin lymphoma and RL (P = 0. 000).Childhood Hodgkin lymphoma is closely correlated with Epstein-Barr virus infection. However, the low rate of EBV infection detected in childhood non-Hodgkin lymphoma might be due to heterogeneous distribution of pathological types in this study.

To study the atopy spectrum and the influence of clinical characteristics upon it in asthmatic children under 4 years of age.Clinical data of 62 asthmatic children under 4 years of age, including age, sex, the age of first wheezing attack, the total times of wheezing attack, the duration of history of wheezing, and the allergic history of both children and parents, were collected. The screening tests on allergens (fx5E, mx2 and Phadiatop) were conducted by fluoroenzyme-immunometric assay using the UniCAP100 system. The total serum IgE level was also measured. Logistic regression was used to analyze the effect of clinical characteristics on allergic sensitization.The positive rates of fx5E, mx2 and Phadiatop were 40.3%, 14.5% and 14.5% respectively, and the total allergic sensitization screening test rate was 46.8%. The sensitization rate to inhalant allergens was 24.2%. The allergic history of parent (s), the sensitization to food allergens, the age of first wheezing attack and total serum IgE level were main factors influencing the sensitization to inhalant allergens.About a quarter of asthmatic children under 4 years of age showed sensitization to inhalant allergens. The asthmatic history of parent (s), the sensitization to food allergens, the age of first wheezing attack greater than 2 years and the significantly higher total serum IgE level may increase the possibility of sensitization to inhalant allergens in asthmatic children under 4 years of age.

To study the efficacy and safety of noninvasive ventilation (NV) for treating children with obstructive sleep apnea.Twenty-one children confirmed obstructive sleep apnea hypopnea syndrome (OSAHS) with full-night polysomnography (PSG) or ambulatory screening device were enrolled in the study. The NV treatment was carried out successfully for all cases. Nasal continuous positive airway pressure (nCPAP) compliance data were gathered via clinical follow-up examination, telephone interview, or mailed questionnaire. The statistical analysis was performed with SPSS 11.0 statistical software. Pre- and on-nCPAP parameters were compared with paired t-test. Twenty-one OSAHS children (17 boys, 4 girls) were enrolled into the study. The mean age of the children was 4. 5 years; ranging from 40 days to 11 years.nCPAP pressure was increased from 4 cm H2O by (1 cm H2O = 0.098 kPa) 0.2 cm H2O each time to the treating pressure which was between 4.8 and 16 cm H2O. Before nCPAP treatment, apnea hypopnea index (AHI) was (80.8 +/- 45.1)/h, the lowest pulse oxygen saturation (SPO2) 0.557 +/- 0.135 and SPO20.90 time during sleep (42.9 +/- 31.9) %, which were much worse compared to that with nCPAP treatment, the above parameters decreased to (6.7 +/- 12.4)/h, 0.862 +/- 0.082, (1.1 +/- 2.5) % respectively(P0.01).Noninvasive ventilation is a safe and effective treatment for OSAHS children. It is possible to use nCPAP as a short-term treatment or as a long-term treatment at home.

This study was to assess certain epidemiological and clinical characteristics of astrovirus infection in children with diarrhea below 5 years old hospitalized at the Beijing Children's Hospital.From September 1999 to August 2001, a total of 288 children with diarrhea below 5 years old hospitalized at Beijing Children's Hospital were studied. Fecal specimens collected from each patient were tested for astrovirus by using enzyme immunoassay (EIA) and further serotyped by reverse-transcription polymerase chain reaction (RT-PCR) using serotype-specific primers.Astrovirus antigen was positive in 9.0% of the patients, and the rate of coinfection with rotavirus was 19.2% among the astrovirus positive patients. The patients with astrovirus infection were at the age of 7 days to 17 months, most (92.3%) of them were less than 12 months. Astrovirus infection occurred mainly between October and March of the following year. Main symptoms included watery stool, vomiting, fever, and dehydration. Increased activity of myocardial enzyme was seen in 4 patients. Of the 22 astrovirus positive specimens, 14 were successfully serotyped by RT-PCR and they were all serotype 1.The overall incidence of astrovirus infection in young children with diarrhea hospitalized at the Beijing Children's Hospital was 9.0%. The predominant serotype was type 1. Astrovirus may play an important role in viral diarrhea in young children in Beijing, China.

To study clinical characteristics of pediatric SARS cases in Beijing.Eighteen pediatric cases with SARS diagnosed on admission were analyzed. The cases were admitted to Beijing Children's Hospital and Ditan Hospital (pediatric ward) from April 8 to May 12.The 18 children aged 5 months to 15 years (10 male and 8 female) had epidemiologically linked findings. Fourteen cases had close contact with SARS patients. Four cases were living in the community where adult SARS patients were found. All the 18 patients but one presented with fever and cough. Most of them had high fever, 2 cases had bradycardia, 2 had diarrhea, and another 2 had tachypnea. Malaise and headache were noted only in 3 cases respectively which were much less frequently seen than in adult patients. Symptoms and signs of the children were much less severe and aggressive than adults cases. Thirteen children had chest radiographic consolidation. Of them, 9 cases had progressive changes after admission, then improved quickly. We did not find significant lower hemoglobin and platelet levels. Most patients had leukopenia and lymphopenia. Serologic test was performed for 15 cases and 8 were positive for SARS virus-IgG and 6 for IgM antibody. Of the 4 cases who had close contact with SARS adults and without chest radiograph abnormal findings, 3 were negative for SARS virus-antibodies. Part of the patients had temporary abnormality of myocardial enzyme and liver function. All these children finally had rapid improvement on chest radiograph. The patients were treated with antiviral agents and corticosteroid. Only two cases required oxygen therapy. No child needed assisted ventilation and no death, nor lung fibrosis occurred. After hospitalization, all patients were improved and discharged when this paper was being written. The average hospital stay of these patients was 14.6 days (6 - 22 days).Compared with adults, pediatric SARS patients seemed to have their own clinical characteristics. The disease in children had lower severity and infectivity than that in adults. The mechanisms of the disease in children should be studied in well-designed clinical trials. Cases like the 4 children who had close contact with SARS adult patients but without chest radiographic changes deserve further studies with the help of more reliable and sensitive etiologic tests.