甲型H1N1流感合并肺炎的影像表现

目的 探讨甲型H1N1流感合并肺炎的影像表现.方法 分析确诊的甲型H1N1流感合并肺炎患者51例,均摄床旁X线胸片,44例同期行胸部CT检查.按肺内病变程度将所有患者分为轻度、中度、重度3型.结果 轻度患者4例,表现为肺内局限片状阴影;中度33例,肺内片状阴影超过2个肺野,其中双侧病变30例,单侧病变3例;重度14例,肺内广泛分布片状及磨玻璃密度阴影,可以合并间质改变,其中2例合并感染,成人呼吸窘迫综合征(ARDS)6例,并发皮下气肿1例.结论 甲型H1N1流感合并肺炎以片状影及磨玻璃密度阴影为主,可见间质病变,合并感染后影像表现多样,部分患者可进展为ARDS.     

甲型H1N1流感胸部高分辨率CT表现

目的 探讨甲型H1N1流感胸部HRCT表现.方法 回顾性分析163例临床确诊为甲型H1N1流感患者的172次胸部HRCT扫描(复查9例)资料,采用标准肺窗和纵隔窗观察图像,分析胸部HRCT影像表现.结果 97例胸部HRCT未见异常,其余66例HRCT主要表现为:(1)肺实质和间质同时受累,磨玻璃密度影35例(53.0%),小叶中心结节30例(45.5%),小叶内间质及小叶间隔增厚31例(47.0%),网状结节影8例(12.1%),单小叶炎症19例(28.8%),实变15例(22.7%),肺不张3例(4.5%),条索影2例(3.0%).(2)胸膜炎症:右侧胸膜炎症8例,左侧胸膜炎症5例,双侧胸膜炎症19例.(3)纵隔淋巴结和腋窝淋巴结肿大7例.(4)抗病毒治疗后病灶吸收快.结论 甲型H1N1流感患者胸部HRCT影像表现多样,类似病毒性肺炎表现,可见肺实质和肺间质炎症、胸膜炎症和纵隔淋巴结肿大.     

民航飞行员感染甲型H1N1流感病毒二例

一、临床资料例1,男性,46岁,民航B737客机机长,飞行时间20 000 h.2009年7月,患者与其儿子(在英国感染了甲型H1N1流感病毒)密切接触7 d后出现"咽痛、发热",体温38.2℃,门诊就医:①行甲型H1N1流感病毒核酸检测;②服用利巴韦林(0.2 g,3次/d)、头孢丙烯咀嚼片(0.25 g,2次/d)治疗.与其儿子密切接触第9天,甲型H1N1流感病毒核酸检测报告为阳性,即刻住院隔离治疗.予口服奥司他韦胶囊治疗5 d(0.15 g,1次/d),服药1 d后体温正常,服药后第10天,甲型H1N1流感病毒核酸检测报告为阴性.痊愈出院.出院后地面观察39 d,恢复飞行.     

北京市输入性甲型H1N1流感病例的流行规律分析

2009年5月16日北京确诊第一例输入性甲型H1N1流感病例.经评估,从第一例甲型H1N1流感病例报告至9月底报告病例数接近北京市实际病例数,本研究采用此时期的甲型H1N1流感数据进行流行病学特点分析,并对此时期所采取的防控措施效果进行初步评价.     

广东省2009年甲型H1N1流感大流第一波人群感染状况分析

目的 了解2009年广东省甲型H1N1流感大流行第一波人群感染状况.方法 采取分层随机抽样方法,按照地区分层(大城市、中小城市和农村)和年龄组分层抽样,抽取调查对象4500人.大城市1500人样本选择在广州市,分布在5个区(每个区选择3个街道);中等城市和农村各抽取1500人,分布在其他20个地市(每个地市抽取1个县,每个区/县至少抽取1个街道和镇,每个街道分别抽取1～2个居委会和村).每个居委会或村按照随机抽样原则选取抽样对象.全部调查对象均未接种甲型H1N1流感疫苗.采用红细胞凝集抑制试验检测人群甲型H1N1流感血清抗体,抗体水平达到1∶40以上为阳性.结果 共调查4319人,调查对象分布在21个市25个县(区)85个街道(镇)144个居委会或村.抗体阳性985人,阳性率为22.82%.询问6月以来是否出现感冒症状,其中无任何症状的人群阳性率为23.47%(471/2007),有其中一项发热、咳嗽、咽痛症状的人群阳性率为26.25%(714/2720),流感样症状的人群阳性率为29.69%(337/1135).结论 广东省甲型H1N1流感大流行第一波人群感染率达22.82%(985/4317),估算自然感染人数为2178万人.     

Dose ranging of adjuvant and antigen in a cell culture H5N1 influenza vaccine: Safety and immunogenicity of a phase 1/2 clinical trial

Background

Dose-sparing strategies and new production technologies will be necessary to produce adequate supplies of vaccines for pandemic influenza. One approach is to include adjuvant, which can reduce the amount of antigen required for immunization and stimulate cross-reactive responses to drifted variants of novel viruses. Dose-sparing studies of adjuvant, itself a finite resource, have not previously been reported for H5N1 vaccine development.

Methodology/principal findings

A total of 753 healthy 18–40-year-old adults were randomized to one of 12 groups (N ∼ 60/group) to receive two intramuscular doses, 21 days apart, of 3.75, 7.5 or 15 μg of cell culture grown influenza A/H5N1 hemagglutinin (A/Indonesia/5/2005 (H5N1)/PR-8-IBCDC-RG2), each dose level formulated with 0%, 25%, 50% or 100% of the MF59 dose contained in licensed influenza vaccine. 752 subjects actually received one dose, and 695 a second dose. Serum hemagglutination inhibition and neutralizing antibody levels, were determined before and 21 days after each dose. Safety and reactogenicity were assessed by self-completed diary cards. Nonadjuvanted H5N1 formulations were poorly immunogenic, but antibody responses were significantly enhanced by all doses of MF59 for each antigen level. The 3.75 μg H5N1 containing 50% MF59 satisfied the European criteria for pandemic vaccine licensure. All formulations were well tolerated, although MF59 dose-dependent increases in the frequency of injection site pain were observed. The frequencies of injection site and systemic reactions were lower after receipt of the second dose of vaccine. No vaccine-related SAE was reported.

Conclusions

Dose-sparing of both antigen and adjuvant is possible without compromising immunogenicity, while improving reactogenicity and is a promising strategy that will expand the availability of vaccines for global control of pandemic influenza.     

Predictors of universal influenza vaccination uptake in grades 1 and 2 Toronto school children: Effective vaccination strategies should not end with at risk children

The first population-based survey to determine predictors of influenza vaccination among children in a major metropolitan city with access to publicly funded health care and a universal influenza immunization program (UIIP). Previously collected demographic and health related data from 5619 school children aged 5–9 in Toronto, in 2006 were used to predict influenza vaccination. Vaccination was more likely in children with current asthma (OR 1.44, 95%CL 1.19–1.75), a high volume of contacts with a health service provider (OR 1.37, 95%CL 1.14–1.65), foreign born children (OR 1.20, 95%CL 1.01–1.42) and those with the lowest income adequacy (OR 1.37, 95%CL 1.12–1.68). Data from this study will be helpful in designing future influenza vaccination strategies to improve vaccination rates in the entire population.     

Safety and immunogenicity of an inactivated split-virus influenza A/H1N1 vaccine in healthy children from 6 months to <18 years of age: A prospective,open-label,multi-center trial

This study was conducted to determine the immunogenicity and safety of an inactivated split-virus influenza A/H1N1 vaccine in healthy Korean children from 6 months to <18 years of age. The immunization schedule consisted of two vaccinations, 21 days apart. The unadjuvanted vaccine contained 7.5 μg (subjects 6 months to <3 years of age) or 15 μg (subjects 3 to <18 years of age) of hemagglutinin antigen per dose. A total of 251 subjects were enrolled and 248 and 242 subjects, respectively, were included in the post-first dose and post-second dose immunogenicity evaluations conducted on a per protocol basis. By day 21, after the first dose, hemagglutination-inhibition titers of 1:40 or more were observed in 5.9% of subjects 6 months to <3 years of age, 34.9% of subjects 3 to <9 years of age and 81.4% of subjects 9–18 years of age. By day 21 after the second dose, the titer had been achieved 55.9%, 69.5% and 90.5%, respectively. No vaccination-related serious adverse events were observed. A single 15-μg dose of vaccine was highly immunogenic in subjects equal to or more than 9 years of age. However, a two-dose regimen is needed to produce potentially protective antibody titers in younger children.     

The Eurocine L3 adjuvants with subunit influenza antigens induce protective immunity in mice after intranasal vaccination

The immunogenicity and protective efficacy in mice of intranasally (i.n.) administrated influenza subunit antigens together with lipid-based adjuvants (Eurocine^®) were compared to those of subcutaneous (s.c.) immunisation. Influenza hemagglutination inhibition (HAI) and ELISA IgG titers were similar in the group's vaccinated s.c. and after i.n. vaccination with adjuvants. The virus-specific IgA levels in serum were higher after vaccination i.n. with adjuvant than after s.c immunisation. Virus-specific IgA was measurable in nasal washings only after i.n vaccinations, with and without adjuvants. Thus, i.n. vaccination with the endogenous non-toxic, lipid adjuvants induced equal or stronger antibody responses as compared to s.c. immunisation with the same antigen. We further analysed the protective efficacy against virus challenge in a mouse model. A subunit antigen preparation of the A/New/Caledonia/20/99 strain was used for vaccination of NMRI mice with different combinations of adjuvants. The mice were challenged i.n. with 6.5 tissue culture infectious doses₅₀ of homologous virus and sacrificed 3 days later. Since the virus is not lethal in mice, the protective efficacy was measured by quantitative, real-time PCR on pulmonary tissue, obtained at autopsy. The mice treated with only adjuvant and the group of naïve mice clearly had the highest mean viral RNA copy numbers (19.200 and 11.000, respectively). All vaccinated groups had significantly lower copy numbers, especially the mice that received the L3A i.n. (−median 120; i.n. L3B − median 2.200; and non-adjuvanted s.c. vaccination − median 2.600). Our findings prompt further investigations of the effect of the formulations in ferrets, monkeys and man.     

Cross-protection against influenza virus infection by intranasal administration of M1-based vaccine with chitosan as an adjuvant

The antigenic variation of influenza virus represents a major health problem, thus continuous efforts have been made to develop broad-spectrum vaccines against influenza virus. Matrix protein 1 (M1) protein is highly conserved in all influenza A strains. In this study, M1 protein was efficiently expressed in Escherichia coli (E. coli), then purified and used for immunization of BALB/c mice by intranasal drip using chitosan as adjuvant. The M1 protein was administered intranasally to mice in combination with chitosan adjuvant twice at an interval of 3 weeks. Three weeks after the second immunization, the mice were challenged with a lethal dose (5 × LD₅₀) of A/Chicken/Jiangsu/7/2002 (H9N2) virus, PR8 (H1N1) virus and A/Chicken/Henan/12/2004 (H5N1) virus. The protective immunity of the vaccine was evaluated by determining the survival rates, residual lung virus titers, bodyweight, and the serum antibody titers of the mice. The results showed that nasal administration of 100 μg M1 in combination with chitosan could not only completely protect the mice effectively against the challenge of the homologous virus but also protect 70% and 30% of the mice against the heterologous H1N1 and H5N1 viruses, respectively. The study indicated that the M1 protein was a candidate antigen for a broad-spectrum influenza virus vaccine and the adjuvant chitosan significantly improved the efficacy of the M1 vaccine.