A群脑膜炎球菌多糖结合疫苗的制备及其稳定性考察

目的 制备安全、有效的A群脑膜炎球菌多糖结合疫苗。方法 将A群脑膜炎球菌多糖以已二酰肼作为多糖和蛋白之间的连接子与精制破伤风类毒素结合，形成A群脑膜炎球菌多糖结合疫苗原液，加保护剂后冻干制成A群脑膜炎球菌多糖结合疫苗，检测其生化、生物学特性和安全性，并考察制品的稳定性。结果 结合疫苗各项检测结果达到质量控制标准，制品放置2年后仍保持稳定。结论 A群脑膜炎球菌多糖结合疫苗制备工艺是可行和稳定的.     

A、C、W135、Y群脑膜炎球菌四价多糖疫苗的安全性和免疫原性研究

目的评价2岁以上正常人群接种A、C、W135、Y群脑膜炎球菌四价多糖疫苗的安全性和免疫原性效果。方法2006年在江苏丹阳市对国内生产的A、C、W135、Y群脑膜炎球菌四价多糖疫苗的安全性和免疫原性进行系统研究,并以兰州生物制品研究所生产的A C群脑膜炎球菌多糖疫苗作对照,用微量杀菌力试验(TTC法)进行A群、C群、W135群、Y群脑膜炎球菌的杀菌抗体检测。结果A、C、W135、Y群脑膜炎球菌多糖疫苗和A C群脑膜炎球菌多糖疫苗分别接种600人和300人,其发热反应率分别为3.5%和3.0%,局部反应率分别为0.83%和1.67%,两组的差异无统计学意义。两组分别有480人和240人采血做杀菌抗体检测,试验疫苗免疫后,各年龄组A群、C群、W135群、Y群杀菌抗体4倍增长率均>90%,与对照疫苗A、C群抗体4倍增长率>90%差异无统计学意义,与对照疫苗W135群、Y群抗体4倍增长率10%及20%左右差异有统计学意义。各年龄组试验疫苗免疫后A群、C群、W135群、Y群杀菌抗体GMT分别为1:351、1:384、1:170和1:280,均达到人群保护水平。结论A、C、W135、Y群脑膜炎球菌多糖疫苗反应轻微,安全性好,免疫原性亦好,可以推广使用。     

关于使用脑膜炎球菌疫苗的建议

预防流行性脑脊髓膜炎（流脑）的有效措施是接种疫苗。目前我国使用的有A群脑膜炎球菌多糖疫苗（Meningococcal Polysaccharide Vaccine,MPV）,A＋C群MPV,A、C、Y、W135群MPV和A＋C群脑膜炎球菌多糖结合疫苗（Meningococcal Polysaccharide Canigate Vaccine,MCV）4个品种。纳入国家免疫规划的是A群MPV和A＋C群MPV。鉴于我国流脑的发病特点和国际上使用脑膜炎球菌疫苗（Meningococcal Vaccine,MenV）的经验,对MenV使用提出以下建议：     

2004 — 2005年我国流行性脑脊髓膜炎病死率分析

接种疫苗是预防流行性脑脊髓膜炎（流脑）最有效、最经济的方法,在过去几十年,随着疫苗的广泛使用,流脑发病率显著下降。目前在中国上市的疫苗主要包括A、C、W、Y群单价和多价多糖脑膜炎球菌疫苗（MPV）,A、C群多糖脑膜炎球菌结合疫苗（MPCV-AC）以及A、C群脑膜炎球菌多糖结合b型流感嗜血杆菌结合联合疫苗（MPCV-AC-hib）。纵观我国脑膜炎球菌疫苗近50年的发展历程,在疫苗生产、质量控制以及相关研究方面均取得了显著成绩,但仍然面临着流脑疾病负担被低估、脑膜炎球菌疫苗免疫策略尚未完善、不同厂家脑膜炎球菌疫苗免疫程序不统一、无B群脑膜炎球菌疫苗上市等问题和挑战,为此应不断提高流脑监测手段及系统开展流脑疾病负担评价的研究以助力我国脑膜炎球菌疫苗免疫策略和免疫程序的完善,并针对流脑血清群高度可变和易发生抗原漂移的特性通过基因重组等技术研发出免疫力更长、保护效果更好的可预防所有血清群流脑的通用性疫苗。     

A、C、Y、W135四群脑膜炎球菌发酵罐培养工艺的研究

目的利用40L发酵罐分别培养四群流行性脑膜炎奈瑟球菌（简称脑膜炎球菌）A、C、Y和W135;优化和比较四种菌的发酵工艺,为开发四价脑膜炎疫苗提供工艺技术。方法通过培养基组成、发酵时间、发酵中补料的形式和补料量,以及搅拌速度、接种密度等培养动力学的研究,比较四种菌培养特性的相同和差异。结果四群流脑球菌的培养特性基本相同,达到最高培养密度的时间及菌体收获率分别为,A和Y群在接种后11 h,收获率均为40%;C群在10 h,收获率30%;W135群在9 h收获率为25%。每种菌对于营养的要求基本相同但在发酵动力学上的差异使补料有所区别。结论发酵罐中采用完全培养基培养,并设定良好的培养条件,及时补充碳源,有利于脑膜炎球菌生长,提高了四价脑膜炎疫苗的产量和质量。     

ACYW135群脑膜炎球菌多糖结合破伤风毒素疫苗免疫学效果的Meta分析

目的 评价ACYW135群脑膜炎球菌多糖结合破伤风毒素疫苗(MPCV-ACYW135-TT)的免疫学效果.方法 检索National Center for Biotechnology Information (NCBI)、Cochrane协作网图书馆、中国生物医学文献数据库、中国期刊全文数据库和万方全文数据库,将有关评价MPCV-ACYW135免疫学效果的随机对照试验(RCT)的研究纳入分析.以接种疫苗1个月后产生的血清杀菌活性(SBA)抗体阳转率(PRR)和几何平均滴度(GMT)作为结局指标,合并不同研究中试验组与对照组间的PRR和GMT的率差(RD)或标准化均数差(SMD).使用RevMan5.1软件进行Meta分析.结果 共纳入13篇文献:有9篇比较了MPCV-ACYW135-TT和ACYW135群脑膜炎球菌多糖疫苗(MPV-ACYW135)之间免疫学效果差异,4篇比较了MPCV-ACYW135-TT和C群脑膜炎球菌多糖结合白喉毒素变异体197疫苗(MPCV-C-CMR197)之间免疫学效果差异.相比于MPV-A-CYW135;受试者在接种MPCV-ACYW135-TT后产生的针对A、C、Y和W135这4个血清型抗体PRR的RD在0.03～0.15之间;产生的针对A、Y和W135这3个血清型抗体GMT的SMD在0.33～1.22之间.1～2岁组幼儿在接种MPCV-ACYW135-TT后产生的针对C群抗体GMT与接种MPCV-C-CMR197差异无统计学意义(H＞0.05).结论 MPCV-ACYW135-TT与其他已上市应用的脑膜炎球菌疫苗有相似的免疫效果.     

A+C群脑膜炎球菌多糖疫苗安全性评估

目的 评估A＋C群脑膜炎球菌多糖疫苗的安全性。方法 以A＋C群脑膜炎球菌多糖疫苗为观察组，伤寒Vi多糖疫苗为对照组，按整群随机分层配对的原则，将研究现场分为108个组群，观察组和对照组各分配54个组。对两组同时建立接种反应监测系统，按统一表格和方法对两组的接种反应进行监测、记录，并进行流行病学调查。结果 两组共接种34543人，其中A＋C群脑膜炎球菌多糖疫苗接种18167人，伤寒Vi疫苗接种16376人。A＋C群脑膜炎球菌多糖疫苗速发接种反应率为0．44‰，一般接种反应率为0．38％o；伤寒Vi疫苗速发接种反应率为0．79％，一般接种反应率为0．73％o；跟踪随访接种反应对象共1239人，其中接种A＋C群脑膜炎球菌多糖疫苗的771人，接种伤寒Vi疫苗的468人。接种后第1天，A＋C群脑膜炎球菌多糖疫苗组的局部反应发生率要明显高于伤寒Vi疫苗（X^2。=13．98，P=0．0002）；接种后第2—3天局部反应和全身反应的发生率，两组差异无统计学意义；两组各自接种人群和未接种人群发热发生率的差异无统计学意义，两组已接种人群的发热发生率差异也无统计学意义；两组均未发现严重反应。结论 A＋C群脑膜炎球菌多糖疫苗与伤寒Vi疫苗均可在不同年龄组人群开展大规模接种，局部及全身接种反应轻微，接种反应率低，有良好的安全性。     

一种国产ACYW135群脑膜炎球菌多糖结合疫苗在3月龄、6-23月龄和2-6岁儿童中的免疫原性

目的评价一种新的国产ACYW135群脑膜炎球菌多糖结合疫苗(MPCV-ACYW)在适龄儿童中的免疫原性。方法采用随机、盲法、同类疫苗对照的非劣效临床试验,在河南省两个地区招募3月龄、6-23月龄A组、6-23月龄B组和2-6岁儿童,分别采用0-1-2月、0-1月、0-3月和1剂次免疫程序接种MPCV-ACYW(试验疫苗)或已上市使用的脑膜炎球菌疫苗(对照疫苗),各年龄组对照疫苗分别为A群C群脑膜炎球菌多糖结合疫苗(MPCV-AC)、另一种MPCV-AC、A群脑膜炎球菌多糖疫苗和ACYW135群脑膜炎球菌多糖疫苗;采用血清体外杀菌试验检测受试者免疫前和全程免疫后30d各群脑膜炎奈瑟菌(Nm)杀菌抗体,比较试验疫苗和对照疫苗抗体阳转率。结果在3月龄儿童中,试验疫苗vs对照疫苗A群、C群Nm抗体阳转率分别为91.42%vs 92.92%(χ~2=0.53,P=0.467)、88.76%vs 87.02%(χ~2=0.48,P=0.489)。在6-23月龄A组儿童中,试验疫苗vs对照疫苗A群、C群Nm抗体阳转率分别为96.80%vs 87.43%(χ~2=20.68,P0.001)、89.24%vs 92.81%(χ~2=2.64,P=0.104)。在6-23月龄B组儿童中,试验疫苗vs对照疫苗A群Nm抗体阳转率为95.86%vs 55.56%(χ~2=111.08,P0.001)。在2-6岁儿童中,试验疫苗vs对照疫苗A群、C群、Y群、W135群Nm抗体阳转率分别为95.89%vs 82.15%(χ~2=28.29,P0.001)、89.04%vs 90.57%(χ~2=0.38,P=0.539)、86.64%vs 50.84%(χ~2=87.60,P0.001)、93.49%vs 54.88%(χ~2=114.16,P0.001)。结论本研究MPCV-ACYW在3月龄、6-23月龄和2-6岁儿童中呈现良好的免疫原性,非劣效于相应的对照疫苗。     

C群脑膜炎奈瑟菌血清杀菌力试验的优化及其应用

目的 优化血清杀菌力试验方法,检测和分析A+C群脑膜炎球菌多糖疫苗接种前后人群血清对C群脑膜炎奈瑟菌(Nm)的杀菌抗体水平.方法 以C群Nm疫苗株(C11)和中国目前C群Nm流行株(053442)作为靶菌,国家Nm标准品测试血清为参考血清,选用Pel-Freez幼兔补体,确定靶菌最适工作浓度.122人接种A+C群脑膜炎球菌多糖疫苗前后分别采集血清标本,共244份,进行C群Nm杀菌抗体水平的检测.结果 菌株C11和053442均可作为靶菌用于血清杀菌力试验;靶菌的工作浓度为A 0.35(600 nm)的菌液稀释4×104倍;A+C群脑膜炎球菌多糖疫苗接种前,122份血清对C11和053442的杀菌抗体几何平均滴度(GMT)分别为1:1.75和1:2.63,人群抗体保护率分别为9.8%和17.2%,A+C群脑膜炎球菌多糖疫苗接种后,122份血清的杀菌抗体GMT和人群保护率均显著升高(P<0.01),对疫苗株和流行株的杀菌抗体GMT分别为1:483.73和1:412.57,保护率分别为100%和95.9%.结论 接种A+C群脑膜炎球菌多糖疫苗,能够显著提高人群对不同亚型的C群Nm的抵抗力,但仍需要针对不同的靶菌进行疫苗免疫效果的监测.     

B群脑膜炎球菌疫苗研究进展

脑膜炎奈瑟菌（Neisseria Meningitidis,Nm）感染仍然严重威胁人群健康,接种疫苗是预防该类疾病的有效手段。根据荚膜多糖的特征,Nm分为A、B、C、W135、Y等不同的血清群。A、C、W135、Y群Nm多糖疫苗以及多糖-蛋白结合疫苗,已经得到广泛应用并证明了其有效性。由于B群Nm菌株的荚膜多糖免疫原性较低,并且与人体神经组织具有同源性,因此B群Nm多糖不能用于疫苗抗原成分。近年来,国际上开展了大量B群Nm蛋白疫苗研究工作,以疫苗外膜蛋白为基础的疫苗研究,以及反向疫苗学技术在B群疫苗研究中的应用,使B群Nm疫苗的研究取得了长足进展。某些B群疫苗显示出良好的免疫原性和有效性,并且已经有B群蛋白疫苗获得许可并规模化应用。     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

The occurrence of antimicrobial substances in toilet,sink and shower drainpipes of clinical units: A neglected source of antibiotic residues

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference.To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02?μg·L^?1 to a maximum of 79?mg·L^?1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.