Immunization-safety monitoring systems for the 2009 H1N1 monovalent influenza vaccination program

The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by many parents as a factor that contributed to their intention to forgo vaccination (see www.hsph.harvard.edu/news/press-releases/2009-releases/survey-40-adults-absolutely-certain-h1n1-vaccine.html and www.med.umich.edu/mott/npch/reports/h1n1.htm). The safety profiles of 2009 H1N1 monovalent influenza vaccines were anticipated to be (and have been) similar to those of seasonal influenza vaccines, for which an excellent safety profile has been demonstrated. Here we describe steps taken by the US government to (1) assess the key federal systems in place before 2009 for monitoring the safety of vaccines and (2) integrate and upgrade those systems for optimal vaccine-safety monitoring during the 2009 H1N1 monovalent influenza vaccination program. These efforts improved monitoring of 2009 H1N1 vaccine safety, hold promise for enhancing future national monitoring of vaccine safety, and may ultimately help improve public confidence in vaccines.     

2009甲型H1N1流感研究进展

2009年3月在墨西哥出现了一种新型甲型H1N1流感病毒,这是一个四源重排的A型流感病毒:来源于猪流感病毒、禽流感病毒及人流感病毒.其临床特点与季节性流感相似,但重症病例可发生在无基础疾病的青壮年人,这与季节性流感不同,其高危人群为患有基础疾病者、孕妇及肥胖者.尽管已经出现了耐药毒株,但奥司他韦治疗仍然有效.该文主要对2009年流行的甲型H1N1流感病毒的基因特点、临床表现及治疗的最新进展进行综述.     

Clinical features of hospitalised children with 2009 H1N1 influenza virus infection

Clinical features and outcome of 2009 H1N1 influenza virus in the paediatric setting is ill-defined. The epidemiologic and clinical features of children with confirmed H1N1 influenza virus infection admitted to an Italian tertiary paediatric hospital from August through December 2009 were evaluated. A total of 63 children (mean age 4.3 years) were studied; of these, 29 (46%) had chronic underlying diseases. The most frequent symptoms and signs at admission were fever (97%), cough (60%) and respiratory disturbances (24%). Forty patients (63.5%) had H1N1-related complications: 32 (51%) pulmonary diseases, three (5%) neurological disorders, such as acute encephalitis or acute disseminated encephalomyelitis, and two (3%) haematological alterations. Three patients were admitted to the Intensive Care Unit. Most children (81%) were treated with oseltamivir: one developed rash during treatment; no other adverse events were noticed. All children survived without sequelae. In conclusions, 2009 H1N1 influenza virus infection in children is associated with a wide spectrum of clinical manifestations. Neurological disorders are not exceptional complications. Oseltamivir therapy seems safe also in infants.     

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.     

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.     

Serum KL‐6 and surfactant protein D in children with 2009 pandemic H1N1 influenza infection

Background: A global pandemic influenza A (H1N1) outbreak occurred in 2009. Rapid progress of respiratory distress is one of the characteristic features of pandemic influenza A (H1N1) infection. The physiologic mechanism causing hypoxia in pandemic influenza A (H1N1) infection, however, has not been elucidated. Methods: The serum levels of KL‐6 and surfactant protein D (SP‐D) were evaluated in 21 cases of pandemic influenza A (H1N1) infection associated with chest radiographic abnormality in order to estimate alveolar involvement. The clinical features were also analyzed. Results: All of the patients had high fever, and rapidly progressed to respiratory distress within several days of disease onset. Despite mild radiographic abnormality in these patients, dyspnea was severe and they had low blood oxygen saturation levels. Many of the patients had a history of allergic diseases including asthma. Serum KL‐6 and SP‐D levels on admission were 191 ± 69 U/mL and 32.6 ± 18.9 ng/mL, respectively. These two levels were still below the upper normal limit 1 week later. There were no clear relationships between specific clinical symptoms and KL‐6 or SP‐D levels. All patients were treated with oseltamivir and/or zanamivir, and improved without mechanical ventilation management. Conclusion: KL‐6 and SP‐D elevation were not significant in pandemic influenza A (H1N1) infection associated with chest radiographic abnormality. In pandemic influenza A (H1N1) infection, alveolar involvement was estimated to be little, and severe respiratory distress was probably caused by obstruction of peripheral bronchi.     

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.     

儿童2009甲型H1N1流感相关神经系统并发症报道

报道儿童2009甲流H1N1流感相关神经系统并发症的临床特征。方法　对深圳市儿童医院2009 - 11 - 04 - 2010 - 01 - 19因2009甲型H1N1流感住院,并发神经系统并发症的21例患儿进行前瞻性调研,对其临床特征及转归进行总结。结果　在150例儿童危重症2009甲型H1N1流感住院患儿中,神经系统并发症的发生率为14.0%（21/150）,其中脑病18例（85.7%）,惊厥2例（9.5%）,脑炎1例（4.7%）。男14例,女7例;年龄中位数为5岁。12例（57%）入住ICU监护,6例（28.5%）接受气管插管及机械通气。17例80.9%）痊愈出院,1例仍在住院,3例（14%）死于脑病。结论　2009甲型H1N1流感相关神经系统并发症发生率高,严重脑病患儿可以导致死亡。随着2009甲型H1N1流感的流行,这一结果应该引起广泛关注。     

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.     

Rapid increase in use of antiviral therapy for hospitalized children with influenza during the 2009 H1N1 epidemic

We used the Pediatric Health Information System to examine annual trends in antiviral prescribing for hospitalized children with influenza before and during the 2009 H1N1 epidemic. During the 2009 H1N1 epidemic, the Centers for Disease Control and Prevention issued recommendations advising antiviral therapy for all hospitalized patients with influenza infection. Before the 2009 H1N1 outbreak, antivirals were prescribed for only 28% of hospitalized children with influenza. This increased sharply to 84% during the 2009 H1N1 period, indicating a favorable response by physicians to clinical guidelines.