儿童甲型H1N1流感的现状、临床特点及处理

目前在全球呈现大流行趋势的甲型H1N1流感病毒是具备高度传染性的病毒,儿童和年轻成年人是主要易患人群,其临床表现相对轻微,但仍有部分病例因出现严重并发症而需要住院治疗.儿童,尤其是小于5岁者,是此次甲型H1N1流感流行中较易成为重症病例的高危人群,容易发生严重并发症,尤其是伴有慢性呼吸道、心血管疾病及免疫缺陷的儿童可能面临更大的死亡危险.神经氨酸酶抑制剂奥司他韦和扎那米韦是目前推荐使用的用于预防和治疗的抗病毒药物.疫苗被认为是控制流行的有效手段.     

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.     

2009 H1N1 Influenza Pandemic

The 2009 H1N1 influenza pandemic took health care workers worldwide by surprise. Early in the course of the pandemic it was determined that children and pregnant women were at high risk of increased morbidity and mortality from the novel influenza virus. The Centers for Disease Control and Prevention and state and local public health officials quickly rallied to develop treatment guidelines for the new strain of influenza A, including emergency approvals for off-label use of some antiviral drugs. Prevention of the spread of influenza via vaccination and environmental controls is critical to the health of children. The 2009 H1N1 influenza virus emerged too late to be included in the 2009/2010 seasonal influenza vaccine, so production of a monovalent vaccine was set in motion. Five months from when the first cases of novel H1N1 appeared in Mexico and the United States, a vaccine was being distributed to high-risk patients. Looking ahead to the 2010/2011 influenza season, it is difficult to predict 2009 H1N1 activity. The 2010/2011 seasonal influenza vaccine will include the 2009 H1N1 strain, so it is critical to get all children vaccinated early in the flu season.     

甲型H1N1流感的研究进展

甲型H1N1流感病毒是人流感病毒基因、禽流感病毒基因和猪流感病毒基因混合的重配株,其造成的疫情来势凶猛,引起世界各国的广泛关注.为了早发现、早诊断、早治疗及有效地预防甲型H1N1流感,本文综述了甲型H1N1流感病毒的特点、流行病学、致人发病的机制、甲型H1N1流感患者的临床表现、实验室检查及有效的治疗和预防措施.     

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.     

Avian flu and possible human pandemic

Avian flu is affecting the poultry animals world over since first outbreak in 1997 in Hong Kong and has resulted in 92 human deaths and culling of more than 150 million poultry animals in Asia and Europe. The loss to the economy has also been enormous. 13 new countries, including India, reported occurrence of the disease in poultry animals in February 2006 only, to the World Health Organisation. This rapid rate of spread of virus along with notoriety of the virus for frequent genetic re-assortment, which might enable H5N1 to infect human beings, threatens of possible influenza pandemic since the last pandemic in 1968. The human influenza caused by this subtype of the virus (H5N1) has high case fatality of 54% and majority of affected humans are between the age of 5 to 23 years. Lack of effective vaccine, poor knowledge about treatment, and with scarcity of public health measures in developing countries are major causes of concern. The real threat of impending pandemic can be avoided only if we act immediately on the basis of currently available source of information and apply scientific knowledge rationally for containment and prevention of bird flu and treat human cases promptly.     

Lessons from the swine flu: Pandemic,panic and/or pandemonium?

The 2009 pandemic of swine-origin A/H1N1 influenza (swine flu) spread rapidly in Australia and there was a prolonged winter outbreak lasting 18 weeks. For Australian children, the case fatality rate of swine flu was no higher than for severe seasonal influenza. Because of the high number of children infected with swine flu, however, there were more children admitted to hospital than usual and more children died. Health-care services (emergency departments, medical wards and intensive care units) were stretched. The introduction of special influenza clinics helped services cope. Pregnant women were at high risk of severe swine flu and seven pregnant women and seven of their babies died. Future pandemic planning should consider severity of influenza, in addition to rapidity of spread, as a criterion for escalating interventions.     

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.     

Perception,attitudes and knowledge regarding the 2009 swine‐origin influenza A (H1N1) virus pandemic among health‐care workers in Australia

Aim: To determine the perceptions, attitudes and knowledge of Australian health‐care workers (HCWs) regarding the novel, swine‐origin influenza A (H1N1) virus (S‐OIV) outbreak that reached the country in early May 2009. Methods: Self‐administered, anonymous Web‐based survey conducted during the early stages of the S‐OIV pandemic. Participants comprised hospital‐ and community‐based medical and nursing staff, medical students, allied health professionals, laboratory staff and administrative personnel. Results: Of the 947 participants surveyed, 59.4% were not convinced that Australia was sufficiently prepared for an influenza pandemic. Only 17.6% of the participants stated they were prepared to work unconditionally during a pandemic; 36.5% stated they would work if they had access to antiviral treatment; 27.9% would if provided with antiviral prophylaxis; and 7.5% would refuse to work. In addition, 37.5% of the participants responded they would refuse or avoid being involved in screening suspected cases. A total of 47.7% admitted to possessing a personal supply of antivirals or having considered this option. Only 48.0% provided a realistic estimate of the mortality associated with an influenza pandemic at a population level. HCWs overestimating the mortality risk and HCWs believing the efficacy of antiviral prophylaxis to be low were significantly less likely to be prepared to work (P= 0.04 and P= 0.0004, respectively). Conclusions: To ensure adequate staffing during an influenza pandemic, preparedness plans should anticipate significant levels of absenteeism by choice. Interventions aimed at increasing staff retention during a pandemic require further evaluation.     

Hematological consequences of pandemic influenza H1N1 infection: a single center experience

Since its identification in April 2009, pandemic influenza H1N1 virus has affected thousands of people worldwide. Viruses, particularly Epstein-Barr virus, cytomegalovirus and parvovirus B19, may have diverse hematological consequences, including anemia, neutropenia, thrombocytopenia, lymphocytosis, hemophagocytic lymphohistiocytosis, and coagulation abnormalities. In this study, a total of 31 consecutive pediatric patients, with and without chronic diseases, who had flu symptoms and were confirmed to have pandemic influenza, were evaluated for hematological consequences upon presentation to hospital. Eight (25.8%) patients had leukopenia and six (19.4%) had thrombocytopenia at the time of diagnosis of H1N1 infection. Pandemic influenza H1N1 infection may cause diverse hematological findings, including cytopenias and hemophagocytosis.     

Benign acute myositis associated with H1N1 influenza A virus infection

We report the clinical and laboratory features of four children with benign acute myositis observed during the current outbreak of the novel H1N1 influenza A virus. Our findings were similar to those of previous reports for benign acute myositis associated with seasonal influenza. No patients needed oseltamivir, and all of them showed quick recovery without recurrences. In the current H1N1 influenza virus pandemic, the diagnosis of benign acute myositis must be suspected in those children with flu symptoms and difficulty to walk, taking this into account might help avoiding unnecessary studies.     

Swine origin influenza (swine flu)

Swine origin influenza was first recognized in the border area of Mexico and United States in April 2009 and during a short span of two months became the first pandemic. The currently circulating strain of swine origin influenza virus of the H1N1 strain has undergone triple reassortment and contains genes from the avian, swine and human viruses. It is transmitted by droplets or fomites. Incubation period is 2 to 7 days. Common clinical symptoms are indistinguishable by any viral respiratory illness, and include fever, cough, sore throat and myalgia. A feature seen more frequently with swine origin influenza is GI upset. Less than 10% of patients require hospitalization. Patients at risk of developing severe disease are - younger than five years, elderly, pregnant women, with chronic systemic illnesses, adolescents on aspirin. Of the severe manifestations of swine origin influenza, pneumonia and respiratory failure are the most common. Unusual symptoms reported are conjunctivitis, parotitis, hemophagocytic syndrome. Infants may present with fever and lethargy with no respiratory symptoms. Diagnosis is based on RT PCR, Viral culture or increasing neutralizing antibodies. Principle of treatment consist of isolation, universal precautions, good infection control practices, supportive care and use of antiviral drugs. Antiviral drugs effective against H1N1 virus include: oseltamivir and zamanavir. With good supportive care case fatality is less than 1%. Preventive measures include: social distancing, practicing respiratory etiquette, hand hygiene and use of chemoprohylaxis with antiviral drugs. Vaccine against H1N1 is not available at present, but will be available in near future.     

Influenza vaccination in India: Position paper of Indian Academy of Pediatrics, 2013

Burden of Influenza is significantly higher in developing countries as compared to developed countries, but the data on the disease burden is less well defined in most of the developing countries including India, and consequently, constraints evolving strategies for prioritization of measures to prevent and control it. The ‘swine flu’ or ‘A(H1N1)’ pandemic is on the wane but the virus continues to circulate causing sporadic outbreaks even in 2013. The A(H1N1)pdm09 has replaced the previous circulating seasonal A (H1N1) virus and acquired the status of a seasonal virus. Limited influenza activity is usually seen throughout the year in India with a clear peaking during the rainy season. The rainy season in the country lasts from June to August in all the regions except Tamil Nadu where it occurs from October to December. IAP recommends the ideal time for offering influenza vaccines is just before the onset of rainy season. The efficacy/effectiveness data of trivalent inactivated influenza vaccines are also presented in different age groups and different categories of individuals. The IAP maintains its earlier recommendations of using the current trivalent inactivated influenza vaccine in all children with risk factors but not as a universal measure. IAP has now prioritized different target groups for influenza vaccination based on contribution of the group to the overall influenza burden, disease severity, and vaccine effectiveness in different age groups and categories. The current trivalent inactivated influenza vaccines incorporate the 2009 pandemic strain also, hence avert the need of a separate ‘A (H1N1)’ vaccine. IAP stresses the need of more refined surveillance; large scale studies on effectiveness of seasonal influenza vaccines in Indian children, and more effective, properly matched, highervalent influenza vaccines.     

Treatment with oseltamivir and prone positioning for a 9‐year‐old boy with ARDS caused by pandemic H1N1 2009 influenza

Here we report the case of a 9‐year‐old boy with acute respiratory distress syndrome (ARDS) caused by novel H1N1 swine‐origin influenza virus A. A diagnosis of ARDS caused by a novel influenza A (H1N1) virus was made on the basis of chest X‐ray and computed tomography together with low oxygenation index (OI) and the detection of novel influenza A (H1N1) virus from tracheal secretion samples. Oseltamivir phosphate and prone positioning were effective in the treatment of ARDS in this case. These findings suggest that anti‐viral drugs and prone positioning can play an important role in the improvement of ARDS caused by novel H1N1 swine‐origin influenza virus A.     

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.     

Swine influenza A (H1N1) virus infection in infants

There are few reports on pandemic swine influenza A (H1N1) virus infection in very young infants. We aimed to discuss the clinical characteristics and management of the H1N1 influenza infection in very young infants. Clinical characteristics of ten infants diagnosed with H1N1 influenza virus infection during the 2009 outbreak season in a tertiary neonatal intensive care unit were evaluated. The diagnosis was confirmed by testing of respiratory samples with pandemic H1N1 influenza specific real-time PCR assay. Of the 46 patients with fever or respiratory problems, ten (22%) were diagnosed with H1N1 influenza virus infection during the 2009 (October?CDecember) peak outbreak season. All infants including the preterms were admitted from home, seven (70%) were full-term and three (30%) were preterm. Median age of the patients at admission was 24.5?days. Fever and cough were the most common symptoms. Apnea was the initial symptoms in three patients. Two patients required oxygen support, one of which, a preterm baby, had been mechanically ventilated for 2?days. Mean duration of hospitalization was 7.8?±?4.9?days. Chest radiography revealed radio-opacities on both lung fields in six patients. In addition, two patients had co-infection. All patients with proven infection were given oseltamivir medication. Recovery was achieved in all patients with no residual deficits or side effects from the antiviral oseltamivir treatment. The H1N1 influenza virus infection in very young infants appears to be mild to moderate in severity. The outcomes of the infants may be influenced by antiviral therapy. Treatment with antiviral oseltamivir appears to have no major adverse effects.     

Hemophagocytic lymphohistiocytosis associated with 2009 pandemic influenza A (H1N1) virus infection

Hemophagocytic lymphohistiocytosis (HLH) has not been described earlier in the context of 2009 pandemic influenza A (H1N1) virus infection, although certain populations are thought to be at risk for complicated pandemic influenza A disease. Here, we report the second case of HLH after infection with the influenza A H1N1 virus treated with peroral oseltamivir successfully.     

Nephrotic Syndrome Following H1N1 Influenza in a 3-Year-Old Boy

Background

The pandemic influenza A/H1N1, spread through the world in 2009, producing a serious epidemic in Italy. Complications are generally limited to patients at the extremes of age (<6 months or >65 years) and those with comorbid medical illness. The most frequent complications of influenza involve the respiratory system.

Case Presentation

A 3-year-old boy with a recent history of upper respiratory tract infection developed a nephrotic syndrome. Together with prednisone, furosemide and albumin bolus, a therapy with oseltamivir was started since the nasopharyngeal swab resulted positive for influenza A/H1N1. Clinical conditions and laboratory findings progressively improved during hospitalization, becoming normal during a 2 month follow up.

Conclusion

The possibility of a renal involvement after influenza A/H1N1 infection should be considered.     

Clinical profile of H1N1 positive HIV-infected children

We report five cases of HIV infected children, who presented with flu-like symptoms and were diagnosed to have H1N1 infection (swine origin influenza). Four of these children were admitted with respiratory distress and pneumonia and were managed in swine flu isolation ICU. Two children required nonivasive ventilatory support. All children recovered completely and at discharge were referred for initiation of ART.