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.     

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.     

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.     

Assessment of parental report for 2009-2010 seasonal and monovalent H1N1 influenza vaccines among children in the emergency department or hospital

ObjectiveTo assess the validity of parental report for seasonal and monovalent H1N1 influenza vaccinations among children 6 months to <18 years who were recommended to receive both vaccines in 2009–2010.MethodsChildren with fever or respiratory symptoms were prospectively enrolled in both emergency departments in Forsyth County, North Carolina, and the only pediatric hospital in the region. Enrollment occurred from September 1, 2009, through April 12, 2010, during the H1N1 influenza pandemic. A parental questionnaire was administered by trained interviewers to ascertain the status of seasonal and monovalent H1N1 influenza vaccines. Parental report was compared with that documented in the medical record and/or the North Carolina immunization registry.ResultsAmong 297 enrolled children 6 months to <18 years of age, 174 (59%) were 6 months to 4 years, 67 (23%) were 5–8 years, and 56 (19%) were 9 to <18 years. Parents reported that 140 (47%) children had received ≥1 dose of 2009–2010 influenza vaccine—128 (43%) for seasonal vaccine and 63 (21%) for H1N1 vaccine. Confirmed vaccination data indicated that 156 (53%) children had received ≥1 dose of any 2009–2010 vaccine—120 (40%) for seasonal vaccine and 53 (18%) for H1N1 vaccine. Parental report of any seasonal influenza vaccination was 92% sensitive and 86% specific and had a kappa of 0.76. Parental report for any H1N1 influenza vaccination was 88% sensitive and 92% specific with a kappa of 0.71.ConclusionsParental report of 2009–2010 seasonal and monovalent H1N1 influenza vaccinations was sensitive and specific and had reasonable agreement with the medical record and/or immunization registry.     

IgG3 deficiency and severity of 2009 pandemic H1N1 influenza

Background: The severity of the 2009 pandemic H1N1 influenza (H1N1 pdm 09) in immune deficient children is unknown. The aim of the present study was to investigate this in a case of complete IgG3 deficiency complicated by pneumonia and asthma attack. Methods: The clinical parameters of the IgG3 deficiency patient were compared with those of four control patients using 95% confidence intervals. These control patients were selected from 71 patients admitted due to pneumonia or bronchitis caused by H1N1 pdm 09, and were chosen according to age, absence of pretreatment with oseltamivir before admission, presence of a past history of asthma, use of antibiotics, and combination of inhalation of a beta2 agonist and treatment with i.v. methylprednisolone for asthma attack. Results: The IgG3 deficiency patient had significantly longer duration of admission and period of oseltamivir, with a significantly decreased pulse oxygen saturation and increased maximum serum C‐reactive protein, creatine kinase and urinary excretion of β2‐microglobulin/creatinine, compared with the controls (P < 0.05). Conclusions: Complete IgG3 deficiency is possibly associated with severity of the clinical course of pneumonia and asthma attack in children suffering from H1N1 pdm 09.     

Myocarditis in a pediatric case of pandemic 2009H1N1 influenza

We report a 6‐year‐old boy with no major disease history or allergic conditions initially presented with pneumonia, progressed to acute respiratory distress syndrome and acute myocarditis caused by pandemic 2009H1N1 influenza diagnosed with RT‐PCR testing, successfully managed with mechanical ventilation and percutaneous cardiopulmonary support system. Marked transient elevation of IgE in acute phase of the disease and the subsequent diagnosis of atopic asthma in our patient suggested a possible role of an underlying allergic condition in the clinicopathological process. Critically ill 2009H1N1‐infected patient with acute respiratory failure should carefully be physiologically monitored together with serial assessment of biomarkers aiming at a favorable cardiac outcome by giving the timely diagnosis and intervention.     

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.     

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.     

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.     

A severely immunocompromised child with uncomplicated oseltamivir-resistant 2009 H1N1 pandemic influenza infection

2009 H1N1 pandemic influenza was associated with increased risk for severe disease in children and the immunosuppressed. We report a case of uncomplicated pneumonia because of infection with oseltamivir-resistant 2009 H1N1 virus in an immunosuppressed pediatric renal transplant patient. Innate immunity and/or altered viral fitness may be responsible for the mild clinical phenotype of the case.