Oseltamivir-resistant 2009 H1N1 influenza pneumonia during therapy in a renal transplant recipient

The emergence of oseltamivir-resistant 2009 H1N1 influenza virus (conferred by the H275Y substitution in NA) during therapy or prophylaxis in immunocompromised patients is a serious concern. The optimal therapy for immunosuppressed patients with oseltamivir-resistant 2009 H1N1 influenza virus is unknown and few options exist. We report a 10-yr-old recipient of kidney transplant who was hospitalized with oseltamivir-resistant 2009 H1N1 influenza pneumonia complicated by severe respiratory failure, ARDS, and renal failure requiring institution of ECMO and CRRT. On presentation, treatment with oseltamivir (second course) and broad-spectrum antibiotics was initiated. Immunosuppressive agents were stopped on hospital day (d) 2. On hospital d 7, given his critical status, immunocompromised state, and difficulty in obtaining intravenous zanamivir, after obtaining ethical approval and parental consent, he was treated with intravenous peramivir (through an Emergency Investigational New Drug Application) for two wk. He tolerated the regimen well and his clinical status improved gradually. Several factors may have contributed to virus clearance and survival including recovery of the immune system, aggressive critical care support, and administration of peramivir. Ongoing surveillance is essential to monitor how oseltamivir-resistant H275Y mutant viruses may evolve in the future.     

H1N1 infection in children with haematological and oncological diseases in Norway

Aim: To describe the impact of H1N1 infections in children with haematological and oncological diseases during the 2009 H1N1 pandemics. Methods: A short questionnaire was e‐mailed to all paediatric departments taking care of patients with oncological and chronic haematological diseases, asking for known cases of H1N1 infections in this patient group. Results: Nine children treated for cancer and seven children with haematological diseases were registered. No death occurred, but two patients treated for cancer (acute lymphoblastic leukaemia at diagnosis, acute myeloid leukaemia in chemotherapy‐induced bone marrow aplasia) experienced life‐threatening respiratory complications. Conclusion: In all patients with haematological disease and most cases of oncological diseases, the infections ran a mild course. However, life‐threatening complications occurred in severely immunosuppressed and neutropenic patients. Delay of anticancer treatment is a concern even in mild cases.     

Acute disseminated encephalomyelitis following 2009 H1N1 influenza vaccine

Acute disseminated encephalomyelitis (ADEM) is an immune‐mediated inflammatory disorder of the central nervous system. We describe a previously healthy 2‐year‐old boy with ADEM, who exhibited high fever, lethargy, and recurrent seizures at 25 days after H1N1 influenza vaccination. To our knowledge, there has been only one report of ADEM following the 2009 H1N1 influenza vaccine, although such vaccination is accompanied with optic neuritis apart from this case. Thus, this is the first case of ADEM without optic neuritis, following the 2009 H1N1 influenza vaccination. Although vaccine‐associated ADEM remains rare, the increasing number of influenza vaccinations might increase the incidence of ADEM. We still need to pay attention to the occurrence of ADEM and treat patients with steroid therapy.     

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.     

Rhabdomyolysis associated with influenza A/H1N1 2009 infection in a pediatric patient

The influenza A/H1N1 2009 epidemic has spread to many countries since 2009, including Japan. We report an immune‐competent child involving rhabdomyolysis and compartment syndrome associated with influenza A/H1N1 2009. The patient was demonstrated rhabdomyolysis with myoglobinuria, hyperkalemia, cardiac dysfunction and compartment syndrome that arose during convalescence from influenza A/H1N1 2009 infection. Although RT‐PCR of muscle tissue yielded negative results for influenza A/H1N1 2009 RNA and no viral positive‐antigen cells were detected in the muscle lesions, the clinical picture suggested rhabdomyolysis associated with influenza A/H1N1. Rhabdomyolysis should be considered in the evaluation of muscle symptoms such as myalgia associated with novel influenza A/H1N1 2009 virus infection, particularly in critically ill patients.     

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.     

Aseptic meningitis in a child due to 2009 pandemic influenza A (H1N1) infection

Neurologic manifestations of seasonal influenza 2009 pandemic influenza A (H1N1) are now known to include encephalitis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, transverse myelitis, and acute necrotizing encephalopathy. We report a case of 2009 pandemic influenza A (H1N1) meningitis in a previously healthy six-year-old girl who presented with fever, headache, abdominal pain, and vomiting. The infection was confirmed via nasopharyngeal and throat swabs. She was treated with oseltamivir successfully. To our knowledge, she is the first child diagnosed as pandemic influenza A (H1N1) meningitis.     

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.     

Hemorrhagic shock and encephalopathy syndrome in a child with pandemic H1N1 2009 influenza virus

We report a case of hemorrhagic shock and encephalopathy in a child with pandemic 2009 H1N1 influenza infection. The patient succumbed within 3 days of admission.     

Neurological complications of pandemic influenza A H1N1 2009 infection: European case series and review

Neurological manifestations and outcomes of children with the 2009 H1N1 virus infection have been reported in three American series and from smaller cohorts and case reports worldwide. Of the 83 children admitted between April 2009 and March 2010 with H1N1 virus infection to a tertiary children’s hospital in a European setting, five children aged between 2 and 10 years had neurological symptoms. Four patients had seizures and encephalopathy at presentation. One patient presented with ataxia; one developed neuropsychiatric manifestations, and two developed movement disorders during the disease course. Early neuroimaging showed evidence of acute necrotising encephalopathy (ANE) in one case and non-specific white matter changes in another. Initial neuroimaging was normal for the other three, but interval MRI showed increased signal in bilateral periventricular distribution in one and significant cerebral volume loss in the other. Clinical outcomes varied: two recovered fully while three had residual seizures and/or significant cognitive deficits. Conclusion An analysis of our patients along with all reported cases reveal that seizures and encephalopathy were common neurological presentations associated with pandemic 2009 H1N1 influenza virus infection in children requiring hospital admission. Neuroimaging suggestive of ANE, basal ganglia involvement and volume loss appears to be associated with worse neurological outcome.     

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.     

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。     

Risk factors for prolonged shedding of 2009 H1N1 influenza virus

This retrospective study was conducted to estimate the shedding of 2009 H1N1 virus and the risk analysis by review of medical charts, laboratory and radiological findings of all inpatients with confirmed pandemic influenza A (H1N1) at a provincial pediatric hospital. A total of 41 cases attending the inpatient department between 15 November, 2009 to 14 December, 2009 were included. Prolonged and discontinuous shedding of 2009 H1N1 virus (median, 10days; range, 2 to 24 days) were detected by real-time RT-PCR. The interval from onset of symptom to the start of oseltamivir therapy was an independent risk factor for prolonged virus shedding.     

儿童2009甲型H1N1流感危重症14例临床特征

目的 分析儿童2009甲型H1N1流感危重症的临床特征.方法 对2009年10月1日至12月25日,我院儿科重症监护病房(PICU)14例2009甲型H1N1流感危重症患儿的临床特征及其预后进行分析.结果 14例平均年龄(4.91±4.14)岁,男女各7例,发病到入院时间为(3.09±1.30)d,从入院到入PICU时间为(0.95±0.96)d,所有患儿均表现出明显的低氧血症,入ICU时平均PaO2/FiO2(氧合指数)为(191.27±80.58)mm Hg(1 mm Hg=0.133 kPa),11例(78.6%)出现ARDS,10例(71.4%)行机械通气,平均通气时间为(12.51±10.03)d,平均ICU住院时间为(12.58±10.65)d,平均rRT-PCR检测甲型H1N1核酸呈阳性时间(17.27±5.57)d;8例(57.1%)患儿有缺铁性贫血、脑瘫和先天性心脏病等基础疾病;CK(肌酸激酶)、CK-MB(肌酸激酶同工酶)、cTnI(肌钙蛋白)和LDH(乳酸脱氢酶)在这些患儿中都有不同程度的升高;入院时第3代死亡危险评分(PRISM Ⅲ)较高和危重病例评分(PCIS)较低的患儿机械通气时间和ICU住院时间较长(P＜0.05).结论 苏州地区儿童2009甲型H1N1流感危重症病情进展快,短时间内即出现显著的低氧血症,甚至ARDS,并伴有不同程度的心肌损害,早期发现不利因素加以干预,是治疗成功的关键.     

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.     

Pandemic A/H1N1(2009) influenza infections in very-low-birth-weight infants--a case series from the German Neonatal Network

6 cases of clinical influenza A/H1N1(2009) infections were reported within the multi-center German Neonatal Network (GNN) during the primary hospital stay in the pandemic season 2009/2010 and 2010/2011. Clinical symptoms varied from transient hyperthermia to apnea and severe respiratory distress. 1 fatal course with systemic inflammatory response after perinatal transmission of A/H1N1(2009) was observed. Oseltamivir treatment in 3/6 infants was without side effects. The reported cases have major implications for the management of VLBW infants: i) fatal courses after perinatal transmission are possible, ii) postnatal A/H1N1(2009) infection may result in life threatening events at a time when the infant is otherwise stable, iii) vaccination should be recommended for parents and medical staff to avoid nosocomial transmission, iv) more data are needed on the benefit and harm of antiviral drugs in preterm infants, v) neonatologists should suspect A/H1N1(2009) infection when unexplained sepsis-like or respiratory symptoms occur in VLBW infants.     

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.