北京季节性甲型流感与2009甲型H1N1流感住院患儿的临床比较

目的 比较因甲型流感病毒(季节性和2009甲型H1N1)感染而住院儿童的流行病学及临床特征.方法 总结回顾分析首都儿科研究所附属儿童医院2003年1月至2010年1月有明确病原学证据的季节性甲型流感组(季节甲流组)和2009甲型H1N1流感组(新型甲流组)感染患儿331例的临床表现、实验室检查等资料.结果 (1)2003年至2008年每年季节甲流组患儿住院的高峰时间在冬季,新型甲流组住院患儿集中在2009年11月至2010年1月.(2)季节甲流组患儿发病年龄中位数为35(22～63)个月,新型甲流组年龄为48(36～67)个月,两组患儿发病年龄有显著差异(Z=-6.702,P＜0.01).(3)季节甲流组和新型甲流组患儿均以发热、咳嗽等流感样症状为主要表现,季节甲流组发热天数5(3～7)d,新型甲流组发热天数6(4～7)d,有显著差异(秩和检验,Z=-7.173,P＜0.01).(4)新型甲流组出现血小板减少,CRP、ALT、CK-MB的升高,以及心电图异常的人数高于季节甲流组.(5)新型甲流组有基础病变患儿60例,其比例高于季节甲流组的25例()(2=12.553,P＜0.01).(6)季节甲流组患肺炎者75例(49.3%),新型甲流组患肺炎者117例(65.4%),后者肺炎患儿人数高于前者(x2=8.661,P＜0.01),重症病例人数明显高于季节甲流组(X2=10.595,P＜0.01),有更高的ICU住院比例(x2=12.873,P＜0.01)和住院天数(Z=-2.764,P＜0.01).结论 2009甲型H1N1流感病毒作为一种新型变异病毒,致病力更强,有基础疾病的患儿更容易被感染,出现肺部、神经及心脏系统的并发症,住院时间长,病死率高.

Abstract：

Objective The novel influenza A (H1N1)virus firstly detected in April 2009 in Mexico rapidly spread to many countries including the United States and Canada where humans were infected with the H1N1 virus and deaths were reported. The pandemic virus strain had never been detected in specimen of human beings and swine. It was so highly contagious and widely spread that threatened life of humans globally. This study aimed to analyze clinical data of hospitalized children patients with 2009 novel H1N1 influenza A virus infection confirmed by etiologic tests, and compared with that of seasonal influenza A. Method Clinical manifestations,laboratory and therapy data from the hospitalized children were collected by designed case report form and analyzed. All patients were enrolled from Capital Institute of Pediatrics from January 2003 to 2010.There were 152 cases in seasonal influenza A group, which was composed of 100 boys and 52 girls. Other 93 boys and 86 girls formed 2009 novel influenza A group.Result Influenza A was dominate from 2003 to 2008 and the peak season was December and January,while the peak hospitalized time of 2009 novel H1N1 influenza was from November 2009 to January 2010. The median age of seasonal influenza group was 35 months,which was lower than that of novel influenza group (Z=-6.702,P＜0.01).Besides,80.9% of the patients in seasonal influenza group were infants,while the novel influenza A group was mainly composed of infants and pre-school children(x2 =40.725,P＜0.01). The cases of both groups had influenza-like symptoms at onset and the most common presentations were fever and cough.The duration of fever was much longer in 2009 novel influenza group(Z=-7.173,P＜0.01). Patients in two groups nearly had the same symptoms except cough was more frequently presented by novel influenza A group cases(x=4.109,P＜0.05).In laboratory examination,the novel influenza group had more cases with abnormality in blood platelet,CRP, ALT, and CK-MB than that of seasonal influenza group (x2=7.562,17.245,4.398,6.217,P＜0.01).Patients in novel influenza A group had more changes in electrocardiogram(x2=24.461,P＜0.01).More patients had common underlying medical condition in novel influenza groups than those in seasonal influenza group(x2=12.553,P＜0.01).Furthermore, the groups had different age distribution in underlying medical diseases(x2=7.231,P＜0.05).Children with 2009 novel H1N1 virus infection tended to catch pneumonia (x2=8.661,P＜0.01)and became the severe cases (x2=10.595,P＜0.01).They had much higher ICU admission rate (x2=12.873,P＜0.01)and longer hospital stay(Z=-2.764,P＜0.01).Conclusion As a new variant of influenza virus A, 2009 novel H1N1 influenza A had stronger pathogenicity. Children with underlying medical conditions had the high risk to be infected and developed severe manifestations.     

Analysis of Fatal Cases of Pandemic Influenza A (H1N1) Virus Infections in Pediatric Patients with Leukemia

Background: Pandemic influenza A/H1N1/2009 virus usually causes mild illness in healthy children. Chronic medical conditions are recognized as increasing the risk for complications of influenza virus infection. Although most studies including children with acute leukemia and H1N1 virus have reported no deaths, some anectodal reports with low patient numbers have reported mortality rates as high as 28.5%. Here, we report patients with leukemia and H1N1 virus and review the literature. Methods: Medical records of all children with leukemia and H1N1 virus in our institution were reviewed for demographic, clinical, and laboratory data. We also carried out a systematic review of the English-language literature. Among the 24 articles found, only patients with leukemia and pandemic H1N1 infections were reviewed by two independent reviewers. Results: Eight of 98 children who received chemotherapy for leukemia were diagnosed with pandemic H1N1 infection. One developed pneumonia and acute respiratory distress syndrome (ARDS) and died. Another one developed hemophagocytic lymphohistiocytosis (HLH) and died due to secondary infection during the 6th week of treatment for HLH. In our study, 2 of 8 patients had a fatal course (25%), compared with an overall mortality of 2.5% in the studies retrieved from PubMed (6/232). Conclusion: Pandemic H1N1 influenza virus caused mortality in patients with ARDS or HLH; an unexpected finding for pandemic H1N1 (2009) influenza virus. Thus, for children with leukemia and infected with H1N1 virus, short- and long-term complications should be kept in mind during evaluation.     

Comparison of influenza A and influenza B virus infection in hospitalized children

BACKGROUND: Influenza A and B viruses were cocirculating in Australia in the winter of 1997. Objective: To compare the clinical and demographic features of children with influenza A or influenza B virus infection admitted to a paediatric tertiary referral centre. METHODOLOGY: Retrospective chart review of 91 hospitalized children with culture-proven influenza A or B virus infection during 1997. RESULTS: Thirty-six (56%) of 64 children with influenza A were under 12 months of age compared with seven (26%) of 27 children with influenza B virus infection (P = 0.02). Influenza B virus infection was more common in children with underlying medical problems (P = 0. 01). Neurological manifestations were present in eight (12.5%) of 64 children with influenza A and none with influenza B virus infection (P = 0.09). There were no significant differences in signs and symptoms of children with influenza A and B virus infection, in severity of illness or in duration of hospital stay. CONCLUSIONS: A greater proportion of children admitted with influenza A virus infection were under 12 months of age. Influenza B virus infection is associated more commonly with underlying medical disorders. It is not possible to differentiate between influenza A or B virus infection from presenting clinical signs and symptoms.     

儿童甲型H1N1流感12例分析

目的 了解儿童甲型H1N1流感的特点.方法 回顾分析2009年5月1日至2009年7月15日复旦大学附属儿科医院发热门诊及病房诊治的12例甲型H1N1流感的流行特征及临床特点;采取患儿鼻咽拭子标本,冰壶保存立即送上海市疾病预防控制中心,采用实时逆转录核酸扩增聚合酶链反应(RT-PCR)进行甲型H1N1流感病毒核酸检测.结果 12例儿童甲型H1N1流感均为输入性病例,5例患儿有明确的甲型H1N1流感患者密切接触史.12例有发热症状,有咳嗽、流涕、食欲不佳症状的各为7例,1例有喘息症状,所有病例均无呕吐和腹泻.11例能准确表述自身感受的患儿中,均无肌肉酸痛,6例有咽痛,3例有腹痛.2例患儿并发肺炎,其中1例患儿病情危重.1例患儿居家隔离对症治疗,11例患儿住院治疗,均参照中国国家卫生部颁布的<甲型HINI流感诊疗方案(2009年试行版第一版)>进行治疗,其中10例息儿接受奥斯他韦抗病毒治疗,未见明显不良反应,所有患儿均痊愈.结论 儿童甲型H1N1流感的症状主要表现为典型的流感症状,大部分患儿临床过程轻微,及时隔离和治疗预后良好,奥斯他韦抗病毒治疗无明显副作用.儿童甲型H1N1流感的流行特征及临床特点尚需要多地区大样本的研究资料.     

2009甲型H1N1流感住院患儿159例分析

目的 探讨因甲型H1N1流感病毒感染住院患儿的临床特征.方法 2009年11月至2010年1月于首都儿科研究所附属儿童医院经实时逆转录-聚合酶链反应(RT-PER)方法确诊的甲型H1N1流感住院患儿159例,男83例,女76例.设计临床资料观察表,逐一记录患儿的临床表现、实验室检查、影像学资料及治疗情况,并进行总结分析.结果 (1)住院患儿5岁以下者占87.4%,54例(34.0%)有基础疾病,婴幼儿组(<3岁,78例)和年长儿组(>3岁,81例)之间重症或危重病例(x2=0.105)、患肺炎比例(x2=0.212)及基础疾病比率(x2=3.383)相近(P均>0.05).(2)患儿均以流感样症状起病,以高热(115例,72.3%)、咳嗽(154例,96.8%)为主,5例危重症患者均出现呼吸困难、紫绀,血气有低氧血症.(3)H1N1流感病毒易侵犯下呼吸道,61.0%患儿出现肺炎,合并细菌感染者21.6%,并可同时有非典型病原体(20例,27.0%)及其他呼吸道病毒(5例,3.1%)感染.单纯甲型H1N1病毒感染组与混合感染组热程相近(t=0.975,P>0.05),混合感染组比单纯感染组更容易发生肺部炎症(x2=4.082,P<0.05),其平均病程及住院天数更长(t=3.182及3.190,P均<0.01).结论 绝大多数患者呼吸道症状轻微,少数病情进展呈现危重症表现.呼吸困难和低氧血症可作为危重症甲型H1N1流感早期症状识别的主要指标,除尽早给予抗病毒治疗外,继发细菌感染者还需覆盖常见病原菌的合理经验用药.     

Factors associated with hypoxemia in children infected with pandemic H1N1 2009 influenza virus

Background: Hypoxemia was found to be a major cause of death from pandemic H1N1 2009 influenza (pH1N1) infection. There are limited data on factors associated with hypoxemia in children infected with pH1N1 influenza virus. Methods: Factors associated with hypoxemia were investigated using univariate and multivariate analysis in 76 hospitalized pediatric patients with laboratory‐confirmed H1N1 influenza virus infection at Gyeongsang National University Hospital in Jinju, South Korea, from August 2009 to January 2010 by retrospective chart review. Results: Hypoxemia occurred in 17 children (22%), of whom three were admitted to an intensive care unit and one died. Hypoxemic patients were significantly more likely to have a higher respiratory rate, pulse rate, white blood cell count (WBC), and C‐reactive protein level, as well as a longer hospital stay. Respiratory rate and WBC count at admission were independently associated with hypoxemia as determined on multivariate analysis, and this association was found to be clinically significant. Conclusion: Although a higher WBC count and respiratory rate may not be specific for pHINI but represent the degree of disease severity for any infectious respiratory disease in general, clinicians can use these parameters at admission as useful, early indicators of disease severity in pediatric pH1N1 infection.     

2009甲型H1N1流感住院患儿多中心临床研究

目的 了解2009年全国多中心2009甲型H1N1流感住院患儿的临床特征,探讨危重症的高危因素和死亡原因.方法 对2009年秋冬季全国17家医院的810例2009甲型H1N1流感住院患儿的临床表现、实验室检查结果以及治疗和转归进行回顾性总结和分析.结果 810例住院患儿中,男508例,女302例,年龄中位数为43个月,其中＜5岁550例(67.9%),合并基础疾病148例(18.5%).常见的表现及例数为:发热780例(96.3%),流涕294例(36.3%),鼻塞192例(23.7%),咽痛147例(18.1%),咳嗽759例(93.7%),咯痰347例(42.8%),喘息219例(27.0%),呼吸困难163例(20.1%),呕吐130例(16.0%),腹泻66例(8.1%),烦躁79例(9.8%),嗜睡64例(7.9%),惊厥32例(4.0%).常见的实验室异常为:外周血白细胞计数增高或降低377例(46.5%),乳酸脱氢酶增高346例(42.7%),C反应蛋白增高306例(37.8%),天冬氨酸转氨酶增高257例(31.7%),肌酸激酶增高174例(21.5%).586例(72.3%)合并肺炎,49例(6.0%)合并脑炎/脑病,30例(3.7%)合并心肌炎.危重症患儿183例,其基础疾病、外周血白细胞计数增高、中性粒细胞比率增高、淋巴细胞比率降低和C反应蛋白增高的发生率明显高于非危重症患儿.19例死亡,占危重患儿的10.4%,8例死于脑炎/脑病,10例主要死于严重肺炎和急性呼吸窘迫综合征,其中5例同时伴有脑炎/脑病,1例死于继发性真菌性脑膜炎.结论 2009甲型H1N1流感容易引起全身多脏器损害.有基础疾病、外周血白细胞计数增高、中性粒细胞比率增高、淋巴细胞比率降低和C反应蛋白增高可能是发生危重症病例的高危因素.合并严重肺炎和急性呼吸窘迫综合征,以及脑炎/脑病是导致死亡的主要因素.     

Natural history of pandemic H1N1 2009 influenza infection in healthy pediatric outpatients

ObjectiveThe pandemic influenza H1N1 2009 (pH1N1) virus is expected to remain a prominent circulating strain in the current and subsequent influenza seasons. The objective of this study was to compare the clinical course of infection with laboratory-confirmed pH1N1 and seasonal influenza A and B in a cohort of previously healthy children managed in the outpatient setting without antiviral therapy.MethodsPreviously healthy children 17 years of age or younger were prospectively enrolled during the first wave of the 2009 pandemic (May–July 2009) and the 2 preceding influenza seasons from a single primary care physician office and a tertiary children’s hospital emergency department. Inclusion criteria were: age ≤17 years; laboratory-confirmed influenza; and not receiving antiviral agents. Follow-up telephone interviews were conducted approximately 2 days and 14 days after presentation to assess symptom duration.ResultsA total of 251 patients (101 with pH1N1, 90 with seasonal influenza A, 60 with seasonal influenza B) were included. Presenting symptoms and duration of symptoms associated with pH1N1 were similar to those with seasonal influenza. Median fever duration in pH1N1 was 3 days and had resolved within 8 days in 95% of patients. Among patients with pH1N1, abnormalities on chest auscultation (10 of 101), the hospitalization rate (2 of 101), the proportion of children receiving intravenous fluid therapy (1 of 101) or supplemental oxygen (1 of 101) were not significantly different from patients with seasonal influenza.ConclusionsIn most children without underlying risk factors for severe influenza, pH1N1 virus causes an uncomplicated respiratory tract illness, no more severe than seasonal influenza.     

Clinical characteristics of children with 2009 pandemic H1N1 influenza virus infections

Background: Further understanding of the clinical manifestations, hospital course and treatment options of the 2009 pandemic H1N1 influenza virus (H1N1) is needed in preparation for future outbreaks. Methods: Seventy‐three children with polymerase‐chain‐reaction‐confirmed infections with H1N1 treated in a tertiary care medical center in Israel were included in the study. Clinical data were extracted from medical records, and analyzed by hospitalization status or the presence of underlying chronic medical conditions. Results: Prevalent symptoms were fever, cough and shortness of breath, with additional findings of conjunctivitis, seizures, chills, dizziness, purpuric rash and chest pain. Hospitalized patients were more likely to have shortness of breath (OR 26.7, 95%CI: 3.5–1150), abnormal lung auscultation (OR 11.6, 95%CI: 2.8–67), abnormal X‐ray (OR 3.3, 95%CI: 1.1–9.6), and a chronic illness (OR 5.4, 95%CI: 1.8–17), compared with non‐hospitalized ones. Disease manifestations were similar between children with or without chronic diseases. Only two (2.7%) children required intensive care, and no deaths were recorded. A high rate (18%) of thrombocytopenia was found. One child had rapid symptom resolution after intravenous immunoglobulin treatment. Conclusion: H1N1 infection follows a mild course, even in the presence of severe underlying diseases. Abnormal respiratory findings and the presence of a chronic disease probably contributed to the decision to hospitalize patients. A rapid resolution of H1N1 symptoms after intravenous immunoglobulin treatment warrants further study, and could be a possible therapeutic option for severe cases.     

Experience of pandemic influenza with H1N1 in children with leukemia

It is not exactly known the risks from infection with pandemic influenza (H1N1) 2009 in children with leukemia. Here the authors present their experience in 5 children with leukemia. Pandemic influenza (H1N1) 2009 was detected in 5 patients (F/M: 3/2) at their institution. The ages of these patients were between 2 and 16 years. Four had acute lymphoblastic leukemia (ALL) and 1 acute myeloblastic leukemia (AML). Three of the ALL patients had the diagnosis of pandemic influenza (H1N1) 2009 at the same time as they were diagnosed with ALL. The remaining 2 patients were receiving intensive chemotherapy. All patients had fever, rhinorrhea, and cough. Although bronchopneumonia was seen in 3 patients, only 1 revealed respiratory distress. Stomach ache and diarrhea was seen in the patient who had no pneumonia. All treated as inpatients, but none of them required hospitalization in intensive care unit. One to 3 days after the symptoms of influenza appeared, oseltamivir (Tamiflu) was given to all patients in combination with broad-spectrum antibiotics. Fever declined to normal ranges in 1 to 3 days after treatment was started. The patients received oseltamivir for 5 to 7 days. Cell culture tests were found to be positive for influenza A and polymerase chain reaction (PCR) revealed H1N1 for all 5 patients. Although this is a very small case series, pandemic influenza (H1N1) 2009 did not seem to be very dangerous for children with leukemia if the oseltamivir treatment was given early when symptoms of influenza appeared.     

Novel inpatient surveillance in tertiary paediatric hospitals in New South Wales illustrates impact of first-wave pandemic influenza A H1N1 (2009) and informs future health service planning

Aim: To document the impact of pandemic influenza A H1N1 (2009) in New South Wales (NSW) children's hospitals. Methods: A novel surveillance system, Paediatric Active Enhanced Disease Surveillance (PAEDS), identified hospitalised children <15 years with laboratory‐proven influenza (1 June–30 September 2009) in the three children's hospitals in NSW: Children's Hospital at Westmead (CHW), Sydney Children's Hospital, John Hunter Children's Hospital. Clinical characteristics, management and complications were documented, and at CHW comparison made with 2007 data. Results: The 324 children identified represented 1802 hospital bed‐days and 230 PICU bed‐days. Most (73.1%) children had H1N1, one had an oseltamivir‐resistant isolate. Median age was 2.5 years: 65% were <5 years. Although 80.9% had cough, 8.0% had no respiratory symptoms. Complications occurred in 34.6%, of whom 56% were previously healthy. Only 50% received antivirals. Forty children (12.3%) were admitted to PICU: one child with H1N1 died. At CHW, comparison between 2009 and 2007 showed nearly twice the total number of admissions (226 vs. 122) and PICU admissions (22 vs. 13), but no deaths either year. Vomiting was more frequent in 2009 than 2007 (38.5% vs. 13.1%; P = 0.0001) as were neurological complications (11.4% vs. 2.4%; P = 0.0027) but length of hospital and PICU stay were similar. Conclusions: PAEDS is a valuable surveillance tool that documented the impact of the H1N1 (2009) pandemic in NSW children's hospitals. High numbers of complications, often in previously well children, suggest an important role for early diagnosis, antiviral therapy and influenza vaccination. Observed regional differences identify areas potentially at greater risk in a subsequent wave.     

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??Objective??To describe the clinical characteristics of neurologic complications associated with 2009 influenza A ??H1N1?? infection in children. Methods??A prospective study of 150 children confirmed 2009 influenza A ??H1N1?? infection in Shenzhen Children Hospital from November 4, 2009, to January 19, 2010 was conducted. The clinical features and outcome of the patients with neurologic complications were analyzed. Results??The incidence rate of neurologic complications associated with 2009 influenza A ??H1N1?? infection was 14% of the hospitalized patients. 18??85.7%?? patients were diagnosed as encephalopathy??2??9.5%?? patients were diagnosed as seizures??1??4.7%?? patient was diagnosed as encephalitis. 14 were male, 7 were female?? the median age was 5 years. 12??57%?? patients were admitted to an ICU, 6??28.5%?? required mechanical ntilation. 17??80.9%?? patients were fully recovered and discharged, three ??14%?? died from severe encephalopathy. Conclusion??The incidence rate of neurologic complications associated with 2009 influenza was high, severe encephalopathy canlead to death. This result should attract a great deal of attention as 2009 influenza A ??H1N1?? pandemic continues.     

Acute childhood encephalitis and encephalopathy associated with influenza: a prospective 11-year review

BACKGROUND: Influenza virus infection has been associated with a variety of neurologic complications. The objective of this study was to evaluate prospectively the role of influenza viruses in acute childhood encephalitis/encephalopathy (ACE). METHODS: All children admitted to the Hospital for Sick Children, Toronto, during an 11-year period with ACE and evidence of acute influenza virus infection were included. Acute influenza virus infection was defined by detection of the organism in the nasopharynx by direct immunofluorescence microscopy or viral culture and/or by a 4-fold or greater rise in complement fixation titer. RESULTS: A total of 311 children with ACE were evaluated; evidence of influenza infection was detected in 7% (22 of 311). Eight were excluded from the main analysis because of evidence implicating other potential pathogens. Eleven of the 14 included subjects were <5 years of age. A respiratory prodrome was documented in 93% of subjects. In 64% neurologic manifestations developed within 5 days of onset of respiratory symptoms. Neuroimaging abnormalities were more common in children <2 years of age. Neurologic sequelae occurred in more than one-half of subjects. CONCLUSIONS: In this prospective registry, influenza virus infection was associated with 5% of ACE cases. The majority of children were <5 years of age and the prevalence of neuroimaging abnormalities was higher in children <2 years of age suggesting that younger children are predisposed to the neurologic complications of influenza. An acute rather than a postinfectious process was suggested by the briefness of the respiratory prodrome in most cases.     

2016—2019年苏州大学附属儿童医院呼吸道感染住院患儿流感监测分析（附742例报告）

目的　探讨苏州大学附属儿童医院呼吸道感染住院患儿流感监测情况。方法　分析2016年1月至2019年12月在苏州大学附属儿童医院呼吸科7322例因急性呼吸道感染（ARTI）住院患儿流感病毒感染资料。采用RT-PCR法进行流感病毒的检测,并进行A/H1N1及A/H3N2、B/Victoria及B/Yamagata的亚型鉴定。结果　（1）7322例住院患儿中,共检出流感病毒阳性742例（10.1％）,2016—2019年各年分别为10.4%、8.6%、6.0%、15.2%。（2）流感病毒-A检出阳性率（6.7%）高于流感病毒-B（3.6%）,以A/H1N1亚型最常见（45.0%）,其他依次为B/Victoria（26.4%）、A/H3N2（19.1%）、B/Yamagata（7.5%）,有4例A/H1N1+B/Yamagata混合感染、10例A/H3N2+ B/Victoria混合感染。（3） ＞3～5岁组流感病毒阳性率最高（14.3%）,其次是＞1～3岁组（12.0%）,流感病毒-B发病年龄［38.0（13.0,56.0）个月］大于流感病毒-A［16.0（7.0,38.0）个月］（Z＝-6.456,P＜0.001）。（4）以冬季阳性检出率最高,占流感总检出率的54.9%,其次是春季（36.0%）,2017年12月至2018年2月有一流行高峰。（5）流感病毒易发生混合感染（64.4％）,最常见的混合感染病原是流感嗜血杆菌（21.2%）,其次是肺炎链球菌（17.5%）和肺炎支原体（15.0%）。（6）95.8%的住院患儿流感合并肺炎,最主要的症状是发热（86.7%）、咳嗽（98.1%）,其次是消化道症状（51.5%）。结论　流感病毒是苏州大学附属儿童医院呼吸道感染住院患儿的重要病原,以A/H1N1亚型最常见,不同年份、季节、月份及年龄流行的流感病毒亚型存在一定差异。＞3～5岁年龄组最多,冬季发病率最高,以肺炎为主要疾病表现,主要临床表现是发热和咳嗽,流感病毒易发生混合感染,多数患者预后良好,均未发生死亡。