单中心住院儿童急性呼吸道感染流行病学调查研究

Epidemiological Investigation of Acute Respiratory Tract Infections in Hospitalized Children at a Single Center

摘要: 目的：通过靶向高通量测序(tNGS)技术调查日照地区住院儿童急性呼吸道感染现状，为本地区儿童呼吸道感染性疾病的预防和治疗提供依据。方法：回顾性队列研究，收集2023年5月至2024年4日照市中医医院因呼吸道感染住院患儿咽拭子/肺泡灌洗液，采用tNGS技术检测常见呼吸道病原体，对检出结果为肺炎支原体(MP)的标本同时进行大环内酯类耐药基因检测，分析不同性别、年龄、月份、季节病原体流行情况，MP耐药情况。研究呼吸道感染发病人数、MP检出情况与温湿度、环境质量(PM2.5指数、SO₂浓度等)的相关性。结果：1755例患儿检出率前5位的病毒依次为：人腺病毒3型10.37%，鼻病毒A型9.63%，人偏肺病毒8.89%、人呼吸道合胞病毒B型8.55%、乙型流感病毒5.93%。检出率前5位的细菌依次为：流感嗜血杆菌36.64%，肺炎链球菌28.83%，鲍曼不动杆菌22.45%，金黄色葡萄球菌18.23%，卡他莫拉菌14.07%。人腺病毒3型、乙型流感病毒、流感嗜血杆菌、鲍曼不动杆菌、金黄色葡萄球菌在学龄期检出率最高，鼻病毒A、人副流感病毒、卡他莫拉菌、肺炎链球菌在学龄前期检出率最高，呼吸道合胞病毒B型在幼儿期检出率最高。除鼻病毒及金黄色葡萄球菌外其他病原体检出率在不同年龄段分布差异均具有统计学意义(P < 0.05)。偏肺病毒、鼻病毒、肺炎链球菌在秋冬季节检出率较高，腺病毒与合胞病毒冬季检出率最高，乙流、流感嗜血杆菌、鲍曼不动杆菌、金黄色葡萄球菌、卡他莫拉菌均在冬春季节检出率较高。检出率最高的病原体是MP (38.6%)，MP耐药基因位点检出率高达98.7% (672/681)，且均为A2063G位点突变。不同年龄组儿童中以学龄期组儿童MP检出率(56.71%)最高。男性、女性检出率分别为36.18%，41.26%；春、夏、秋、冬四季阳性率分别为29.79%、20.75%、45.36%、50.93%。MP检出率在年龄、性别、季节分布差异均有统计学意义(P < 0.05)。每月MP检出次数与SO₂浓度呈中度正向线性相关、与CO浓度呈强正向线性相关；其中每月送检样本总数与PM2.5指数、SO₂浓度、CO浓度呈极强正向直线相关，与PM10指数、NO₂浓度呈强正向线性相关，与O₃浓度呈极强负向线性相关，与温度呈强负向线性相关，与湿度呈中度负向线性相关。结论：调查期间日照地区住院儿童呼吸道感染检出率较高的病毒有：人腺病毒3型、鼻病毒A型、人偏肺病毒、人呼吸道合胞病毒B型、乙型流感病毒。检出率较高的细菌有：流感嗜血杆菌、肺炎链球菌、鲍曼不动杆菌、金黄色葡萄球菌、卡他莫拉菌。检出率最高的病原体是MP，MP对大环内酯类耐药率高达98.7%，均为耐药基因位点A2063G突变。病原体检出率、分布与年龄、性别、时间有一定相关性。儿童呼吸道感染发病人数与环境质量及温湿度有相关性。MP检出率与环境质量、温湿度无显著相关性。

Abstract: Objective: We used targeted next-generation sequencing (tNGS) technology to investigate the current situation of acute respiratory tract infections in hospitalized children in Rizhao area, and to provide a basis for the prevention and treatment of pediatric respiratory infectious diseases in children in this area. Method: A retrospective cohort study was carried out. Throat swabs or alveolar lavage fluids were collected from children hospitalized for respiratory tract infections at Rizhao Traditional Chinese Medicine Hospital from May 2023 to April 2024. Common respiratory pathogens were detected by means of tNGS technology. Macrolide resistance gene detection was simultaneously performed on specimens with a positive detection result for Mycoplasma pneumoniae (MP). The prevalence of pathogens among different genders, ages, months, and seasons was analyzed, along with the drug resistance of MP. The correlation between the number of respiratory infection cases, MP detection rate, and temperature, humidity and environmental quality (such as the PM2.5 index and SO₂ concentration) was investigated. Result: Among the 1755 children patients, the top 5 viruses in terms of detection rate were as follows: hadv-3 10.37%, rhinovirus A 9.63%, human metapneumovirus 8.89%, RSV-B 8.55%, and Influenza B virus 5.93%. The top five bacteria in terms of detection rates are, in sequence: Haemophilus influenzae 36.64%, Streptococcus pneumoniae 28.83%, Acinetobacter baumannii 22.45%, Staphylococcus aureus 18.23%, and Moraxella catarrhalis 14.07%. hadv-3, influenza B virus, Haemophilus influenzae, Acinetobacter baumannii and Staphylococcus aureus have the highest detection rates during the school age. Rhinovirus A, human parainfluenza virus, Moraxella catarrhalis and Streptococcus pneumoniae have the highest detection rates before the school age. RSV-B has the highest detection rate during early childhood. Except for rhinovirus, Staphylococcus aureus, the detection rates of other pathogens and their age distribution differences are statistically significant (P < 0.05). The detection rates of metapneumovirus, rhinovirus, and Streptococcus pneumoniae are relatively high in autumn and winter. The detection rates of adenovirus and syncytial virus peak in winter. Influenza B, Haemophilus influenzae, Acinetobacter baumannii, Staphylococcus aureus, and Moraxella catarrhalis all have relatively high detection rates in winter and spring. The pathogen with the highest detection rate is MP (38.6%). The detection rate of the MP resistance gene locus is as high as 98.7% (672/681), and all are mutations at the A2063G locus. Among different age groups of children, the detection rate of MP is the highest in the school-age group (56.71%). The detection rates in males and females are 36.18% and 41.26% respectively. The positive rates in spring, summer, autumn, and winter are 29.79%, 20.75%, 45.36%, and 50.93% respectively. Statistically significant differences were observed in the age, gender, and seasonal distribution of Mycoplasma pneumoniae (MP) detection rates among child patients (P < 0.05). The monthly detection frequency of MP was moderately positively linearly correlated with the concentration of sulfur dioxide (SO₂) and strongly positively linearly correlated with the concentration of carbon monoxide (CO). Among them, the total number of samples sent for inspection each month showed a very strong positive linear correlation with PM2.5 index, SO₂ concentration and CO concentration, a strong positive linear correlation with PM10 index and NO₂ concentration, a very strong negative linear correlation with O₃ concentration, a strong negative linear correlation with temperature, and a moderate negative linear correlation with humidity. Conclusion: During the investigation period, the viruses with relatively high detection rates of respiratory tract infections among hospitalized children in the Rizhao area were hadv-3, rhinovirus type A, human metapneumovirus, RSV-B, and influenza B virus. The bacteria with relatively high detection rates were Haemophilus influenzae, Streptococcus pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, and Moraxella catarrhalis. The pathogen with the highest detection rate was MP. The resistance rate of MP to macrolides was as high as 98.7%, and all of these were mutations at the resistance gene locus A2063G. The detection rate and distribution of pathogens have certain correlation with age, time, and gender. The incidence of respiratory tract infections in children is related to environmental quality, temperature, and humidity. However, the detection rate of MP shows no significant correlation with environmental quality, temperature, or humidity.