Child ; Humans ; Case-Control Studies ; East Asian People ; Genetic Predisposition to Disease/genetics* ; Methyltransferases/genetics* ; Polymorphism, Genetic ; Wilms Tumor/pathology*

Acute respiratory tract infection is the most common infectious disease in children, which seriously threatens children′s health.Rapid and accurate etiological diagnosis is of great significance for the clinical treatment and control of these diseases.Pathogen nucleic acid test was applied and became the main method of respiratory tract infection diagnosis for its high sensitivity and specificity.To regulate the application of pathogen nucleic acid amplification test in respiratory tract infection in children, improve the diagnosis level, expert consensus on nucleic acid amplification test of respiratory pathogens in children was prepared to guide the application and promote pathogens diagnosis ability.

Objective:To understand the characters of norovirus infection in children with acute diarrhea in Beijing from 2014 to 2019.Methods:Fecal specimens were collected from children with acute diarrhea visiting the hospital affiliated to the Capital Institute of Pediatrics from April 2014 to December 2019 for norovirus screening by reverse transcription-polymerase chain reaction (RT-PCR). Then RdRp gene and VP1 gene of norovirus (NoV) were amplified and sequenced from positive specimens and then genotyped by Norovirus Genotyping Tool 2.0.Results:Fecal specimens were collected from 2 577 cases with acute diarrhea and tested for NoV RNA in this study, of which 484 cases (18.78%, 484/2 577) were positive for NoV. NoV infection can occur all year round, with obvious seasonal distribution, the epidemic peak is in autumn and winter. There was no gender difference in the detection of NoV ( χ2=1.77, P=0.183). 399 specimens genotyped by VP1 gene with 98.25% (392/399) being GII and GII.4 Sydney as the mainly genotype (52.13%, 208/399), followed by GII.3 (19.8%, 79/399) and GII.2 (18.5%, 74/399). Then 267 specimens also were genotyped by RdRp region, which revealed that the main genotype was GII.P31 (57.3 %, 153/267), followed by GII.P12 (15.36%, 41/267) and GII.P16 (14.98 %, 40/267). Dual-typing revealed that various combination strains, GII.4 Sydney[P31] (53.18%, 142/267) as the major combination, followed by GII.3[P12] and GII.2[P16] (15.36%, 41/267 and 10.49%, 28/267). While GII.3[P12] showed a downward trend, GII.4 Sydney[P16] increased gradually. Conclusions:Norovirus is an important pathogen of acute diarrhea in children in Beijing, from 2014 to 2019, with various prevalent genotypes.

Objective:To investigate the spectrum of pathogenic agents in pediatric patients with acute respiratory infections (ARI) during the outbreak of coronavirus infectious diseases 2019 (COVID-19).Methods:Three groups of children were enrolled into the prospective study during January 20 to February 20, 2020 from Capital Institute of Pediatrics, including children in the exposed group with ARI and epidemiological history associated with COVID-19 from whom both pharyngeal and nasopharyngeal swabs were collected, children in the ARI group without COVID-19 associated epidemiological history and children in the screening group for hospital admission, with neither COVID-19 associated epidemiological history nor ARI. Only nasopharyngeal swabs were collected in the ARI group and screening group. Each group is expected to include at least 30 cases. All specimens were tested for 2019-nCoV nucleic acid by two diagnostic kits from different manufacturers. All nasopharyngeal swabs were tested for multiple respiratory pathogens, whilst the results from the ARI group were compared with that in the correspondence periods of 2019 and 2018 used by t or χ 2 test. Results:A total of 244 children were enrolled into three groups, including 139 males and 105 females, the age was (5±4) years. The test of 2019-nCoV nucleic acid were negative in all children, and high positive rates of pathogens were detected in exposed (69.4%, 25/36) and ARI (55.3%, 73/132) groups, with the highest positive rate for mycoplasma pneumoniae (MP) (19.4%, 7/36 and 17.4%, 23/132, respectively), followed by human metapneumovirus (hMPV) (16.7%, 6/36 and 9.8%, 13/132, respectively). The positive rate (11.8%, 9/76) of pathogens in the screening group was low. In the same period of 2019, the positive rate of pathogens was 83.7% (77/92), with the highest rates for respiratory syncytial virus (RSV) A (29.3%, 27/92), followed by influenza virus (Flu) A (H1N1) (19.6%, 18/92) and adenovirus (ADV) (14.1%, 13/92), which showed significant difference with the positive rates of the three viruses in 2020 (RSV A: χ 2=27.346, P<0.01; FluA (H1N1): χ 2=28.083, P<0.01; ADV: χ 2=7.848, P=0.005) . In 2018, the positive rate of pathogens was 61.0% (50/82), with the highest rate for human bocavirus (HBoV) (13.4%, 11/82) and followed by ADV (11.0%, 9/82), and significant difference was shown in the positive rate of HBoV with that in 2020 (χ 2=6.776, P=0.009). Conclusions:The infection rate of 2019-nCoV is low among children in Beijing with no family clustering or no close contact, even with epidemiological history. The spectrum of pathogens of ARI in children during the research period is quite different from that in the previous years when the viral infections were dominant. MP is the highest positively detected one among the main pathogens during the outbreak of COVID-19 in Beijing where there is no main outbreak area.

Objective: To study the clinical characteristics of children with adenovirus pneumonia and provide evidence for clinical diagnosis and treatment timely. Method: This retrospective study included 89 children who were confirmed to have adenovirus pneumonia in hospital from January 2015 to December 2016. All the immunofluorescence test result of the 89 children showed that the exfoliated nasopharyngeal cells from the 89 children were all adenovirus antigen positive. All the severe type children reached the diagnostic criteria of severe pneumonia by the respiratory group in the society of pediatrics, Chinese Medical Association. The children were divided into 2 groups (severe type group and common type group). Different factors such as epidemiologic feature, clinical manifestation, laboratory examination and imaging data were analyzed. Results: Among the 89 pediatric patients, the male to female ratio was 1.5∶1. The ages ranged from 1 month to 14 years. Children under 5 years of age accounted for 96.6%(86/89). The incidence was 37.1%(33/89)in winter and 30.3%(27/89)in spring. The lengths of hospital stay were 3-48 days and the median length of stay was 8.25±4.75 days. All of these 89 cases had fever and cough. The proportion of severe adenovirus pneumonia was high among male, under 2 years of age, those with dyspnea, hepatosplenomegaly, tachycardia, leukocytosis, elevated C-reactive protein (CRP), PCT, myocardial enzymes, electrocardiogram abnormality and cluster shadow in chest CT. Differences were statistically significant (P<0.05). Conclusions Special attention should be paid to the male children under the 2 years of age with abnormal related indicators to consider severe adenovirus pneumonia. Early detection and treatment are the key to improve treatment and reduce death.

Objective: To analyze and compare the epidemiological features of prevalent influenza A viruses in children in Beijing during 13 consecutive surveillance seasons from 2004 to 2017. Methods: This was a repeated cross section study. Throat swabs were collected weekly from children with influenza-like illnesses (ILI) who presented to the outpatient/emergency department of Children's Hospital, Capital Institute of Pediatrics during the period from September, 2004 to August, 2017. All of the specimens were inoculated into Madin Darby canine kidney (MDCK) cells to isolate influenza viruses followed by identifying different types of influenza viruses with reference antisera by hemagglutination-inhibition assay. Descriptive statistics, t test and chi-square test were used to analyze the characteristics of prevalent influenza and characteristics of children infected with different types of influenza viruses. Results: Out of 10 984 specimens from ILI tested for influenza viruses, 1 052 (9.6%) were positive for influenza A viruses, and the positive rate was higher than that of influenza B viruses (6.7%, 741/10 984). Out of 1 052 cases positive for influenza A viruses, 70 cases of seasonal H1N1, 302 cases of 2 009 pandemic H1N1 and 680 cases of H3N2 were identified. The mean age of children with influenza A was (4.2±2.9) years, in whom 55.5% (584/1 052) were male. The mean age of children infected with seasonal H1N1, 2009 pandemic H1N1 and H3N2 was (4.6±2.1) , (4.3±3.1) and (4.2±2.9) years, respectively. There was no significant difference in the mean age among children infected with different subtypes of influenza A viruses (seasonal H1N1 vs. H3N2: t=1.139, P=0.255; 2009 pandemic H1N1 vs. H3N2: t=0.631, P=0.528; seasonal H1N1 vs. 2009 pandemic H1N1: t=0.720, P=0.472), while the mean age of children with influenza B was higher than that of the patients with influenza A ((5.2±2.7) vs. (4.2±2.9) years, t=7.120, P=0.000). The infection rate of influenza A in children with each age group was significantly different from that of influenza B. The infection rate of 2009 pandemic H1N1 and H3N2 increased with age, except for the patients of 0-6 months. Meanwhile, the infection rate of H3N2 in children aged 6 months to 12 years was higher than that of seasonal H1N1 and 2009 pandemic H1N1 (all P<0.05). The influenza A epidemic peaked earlier than that of influenza B when the positive rate of influenza A was higher than that of influenza B, and vice versa. After 2009, circulating strain was substituted by 2009 pandemic H1N1 virus with higher positive rate, while previous seasonal H1N1 had not been detected. The 2009 pandemic H1N1 circulated at high level in two consecutive seasons, which was followed by low level in next season. H3N2 epidemic peaked mostly in winter and spring each year, however, the epidemic wave of H3N2 with high virulence occurred so early in the summer in the year of 2009 H1N1 pandemic. Conclusions The characteristics of prevalent influenza A viruses in children were different among 13 surveillance seasons from 2004 to 2017 in Beijing. The 2009 pandemic H1N1 and H3N2 became the predominant strains of influenza A virus.

Objective: To evaluate the clinical value of a rapid respiratory syncytial virus (RSV) antigen detection in point-of-care testing (POCT). Method: A total of 209 specimens, including 78 throat swabs (TS) and 131 nasopharyngeal aspirates (NPAs), were collected from inpatients who visited the Children′s Hospital Affiliated to the Capital Institute of Pediatrics and were diagnosed as acute respiratory infection from 5 January to 7 February, 2015. These specimens were tested for RSV by a rapid antigen detection kit which was compared with reverse transcription polymerase chain reaction (RT-PCR) and direct immunofluorescence assay (DFA) for RSV detection. Result: Compared with DFA for NPAs, the sensitivity and specificity of rapid antigen detection were 83.9% and 97.3%, respectively, with Kappa value of 0.86; Compared with RT-PCR, the sensitivity (NPAs, 74.2%; TS, 77.8%) and specificity (NPAs, 100.0%; TS, 92.0%) of rapid antigen detection were high, too, with Kappa value of 0.74 in NPAs and 0.62 in TS. However, the RSV positive rate of rapid antigen detection in TS (21.7%) from pediatric patients with acute lower respiratory tract infection was lower than that in NPAs (78.3%), as well as that of RT-PCR (7.3% in TS verse 78% in NPAs). The RSV rapid antigen detection kit can be finished in about 10 minutes. Conclusion With characteristics of high specificity, high sensitivity, being rapid, efficient and easy to operate in comparison with DFA and RT-PCR, RSV rapid antigen detection in this study is suitable for POCT. For pediatric patients with acute respiratory tract infection, NPA was better than TS for RSV detection.

Objective: To investigate the clinical characteristics of respiratory syncytial virus(RSV)bronchiolitis and molecular biological characteristics of RSV in children in Beijing. Method: In a systematic retrospective study, 2 296 nasopharyngeal aspirates (NPA) were collected from children diagnosed with bronchiolitis from July 2006 to June 2016 for respiratory virus screening using direct immunofluorescence assay (DFA). For specimens positive for RSV, subgroup A or B was confirmed by real time RT-PCR and genotype of RSV was determined by amplifying the full G glycoprotein gene and sequencing. Clinical data were evaluated by the modified Tal score to compare the severity between RSV subtypes, as well as genotypes. Statistical analyses were performed using t test, Mann-Whitney U test and χ² test. Result: In 2 296 bronchiolitis cases, 961(41.9%) were RSV positive, including 719(74.8%) RSV A and 236 (24.6%) RSV B. The dominant RSV subtype changed from year to year: A-A-B-B-A-A-B-AB-A-AB and more bronchiolitis cases were identified in RSV A dominant years. Six genotypes of RSV A (NA1, NA2, NA3, NA4, GA5 and ON1) and 5 genotypes of RSV B (BA3, BA7, BA9, BA10 and CB1) were prevalent in Beijing. The dominant genotypes of RSV A were NA1 (55.9%) with high rates (50.0%-100%) before 2014 and ON1 (39.1%), mainly detected after 2014, while BA9 (90.6%) was the absolute dominant RSV B genotype. No significant difference in the severity of bronchiolitis was shown between cases of RSV A and B. Children positive for NA1 were more likely to stay longer in hospital (Median time: 8 days) compared to the group positive for ON1(Median time: 6 days ) (U=1.035, P=0.005) and had higher proportion of moderate to severe degree symptoms (Moderate: 41.0%, Severe: 10.0%) compared with ON1 group (Moderate: 22.9%, Severe: 4.3%) (U=9.785, P=0.008). In the group positive for ON1, more children had fever (ON1: 38.6%, NA1: 15.0%) (χ²=11.064, P=0.001) and more were younger than 3 months(ON1: 54.3%, NA1: 33.0%) (χ²=77.408, P<0.001). Conclusion The dominant RSV subgroup changed from year to year with a shifting pattern. The correlation between RSV genotypes and the severity of disease was documented in the study.

Objective To evaluate the clinical value of a rapid respiratory syncytial virus ( RSV ) antigen detection in point-of-care testing (POCT).Method A total of 209 specimens, including 78 throat swabs (TS) and 131 nasopharyngeal aspirates ( NPAs), were collected from inpatients who visited the Children′s Hospital Affiliated to the Capital Institute of Pediatrics and were diagnosed as acute respiratory infection from 5 January to 7 February , 2015.These specimens were tested for RSV by a rapid antigen detection kit which was compared with reverse transcription polymerase chain reaction ( RT-PCR) and direct immunofluorescence assay ( DFA ) for RSV detection. Result Compared with DFA for NPAs , the sensitivity and specificity of rapid antigen detection were 83.9% and 97.3%, respectively , with Kappa value of 0.86; Compared with RT-PCR, the sensitivity ( NPAs, 74.2%; TS, 77.8%) and specificity ( NPAs, 100.0%;TS, 92.0%) of rapid antigen detection were high , too, with Kappa value of 0.74 in NPAs and 0.62 in TS.However , the RSV positive rate of rapid antigen detection in TS ( 21.7%) from pediatric patients with acute lower respiratory tract infection was lower than that in NPAs (78.3%), as well as that of RT-PCR (7.3%in TS verse 78%in NPAs).The RSV rapid antigen detection kit can be finished in about 10 minutes.Conclusion With characteristics of high specificity , high sensitivity , being rapid , efficient and easy to operate in comparison with DFA and RT-PCR, RSV rapid antigen detection in this study is suitable for POCT.For pediatric patients with acute respiratory tract infection , NPA was better than TS for RSV detection.

Objective To compare the prevalence characteristics of influenza viruses in children in Beijing during 2014-2015 and 2015-2016 influenza seasons.Method Throat swabs were collected weekly from children with influenza-like illnesses who visited in Children's Hospital affiliated to Capital Institute of Pediatrics during the period from September 2014 to May 2016.Influenza viruses A and B viruses were detected by real-time RT-PCR,followed by identification of H3 N2,H 1N 1 pdm,B/Victoria-like and B/ Yamagata-like.The prevalence characteristics of influenza viruses was estimated by means of descriptive statistics.The t test and chi-square test were used to compare median age and gender ratio of infected children among different types of influenza viruses.Result Out of 1 821 throat swabs collected,139 (7.6％) were positive for H3N2 and 43 (2.4％) for H1N1pdm and 204 (11.2％) for influenza B virus,including 108 for B/Victoria-like and 96 for B/Yamagata-like.The median age of H1N1pdm infected children ((3.3 ± 2.2) years) was significantly younger than that of H3N2 ((4.7 ± 3.2) years) and influenza B virus ((4.9 ± 2.8) years) (H1 N1 pdm vs.H3N2:t =2.848,P =0.002;H1N1 pdm vs.influenza B,t =3.682,P =0.000).Two epidemic peaks were presented in 2014-2015 influenza season,dominated definitely by H3N2 and B/Yamagata-like,respectively,while one delayed peak started at the 51st week,2015,co-circulated with H3N2,Hl Nlpdm and influenza B viruses,among which B/Victoria-like virus was predominant during the 2015-2016 season.Conclusion Prevalence characteristics of influenza viruses are different between 2014-2015 and 2015-2016 influenza seasonal epidemics in children in Beijing.It is important to monitor the genetic variations of influenza viruses and to keep close attention to influenza B virus as well as influenza A virus.