人用狂犬病疫苗的不良反应分析

目的探讨人用狂犬病疫苗接种后的不良反应发生情况。方法收集2009年~2015年接种的800例狂犬病疫苗的人员发生的120例不良反应人员,本组资料采用的狂犬疫苗有进口冻干人用狂犬病疫苗(Vero细胞)、国产冻干人用狂犬病疫苗(Vero细胞)、国产液体人用狂犬病疫苗(Vero细胞)三种。严格按照接种程序进行接种。对发生不良反应的人员进行总结和分析。结果 2009年~2015年接种的800例狂犬病疫苗的人员发生的120例不良反应人员,不良反应发生率为15.0%。其中局部反应50例,占6.25%,全身反应70例,占8.75%,根据疫苗种类的不同,进口冻干人用狂犬病疫苗接种500例,发生不良反应12例,不良反应发生率为10.9%,且均为局部反应,国产冻干人用狂犬病疫苗接种190例,发生不良反应28例,不良反应发生率为14.7%,且均为局部反应,国产液体人用狂犬病疫苗接种110例,发生不良反应80例,不良反应发生率为16.0%,其中局部不良反应10例,全身不良反应70例。结论人用狂犬病疫苗的不良反应率高,且国产冻干和进口冻干狂犬病疫苗以局部不良反应为主,国产冻干人用狂犬病疫苗与国产液体人用狂犬病疫苗不良反应发生率较差异不大,国产产液体人用狂犬病疫苗不良反应表现较重,出现全身反应例数不少。     

费休氏容量法测量冻干人用狂犬病疫苗中水分含量的不确定度分析

目的对费休氏容量法测量冻干人用狂犬病疫苗中水分含量的不确定度进行分析,为评价该方法的准确性和可靠性提供科学依据。方法建立费休氏容量法测量冻干人用狂犬病疫苗中水分含量的数学模型,找出影响不确定度的因素,并对各个不确定度分量进行评估。结果计算出各变量的不确定度,取包含因子K=2,置信概率为95%,费休氏容量法测量冻干人用狂犬病疫苗中水分含量的扩展不确定度为0.082%。结论卡尔费休容量法检测冻干人用狂犬疫苗中水分含量时,不确定度主要由测定时卡尔费休试液的消耗体积和滴定度F值产生,该评价方法适用于冻干狂犬疫苗水分测定的不确定度评定与报告。     

儿童接种狂犬病纯化疫苗的免疫效果和安全性观察

目的 观察狂犬病纯化疫苗在儿童中的免疫效果和安全性.方法 对注射狂犬病疫苗的337例儿童进行观察并应用酶联免疫吸附法进行血清抗体检测.结果 接种疫苗后阳性率达99.7%,不良反应轻微.结论 国产无佐剂液体疫苗、国产冻干疫苗及进口冻干疫苗对儿童均具有良好的免疫原性,阳性率满意,安全性好.     

冻干Vero细胞狂犬病纯化疫苗在120例门诊病人中的临床效果

目的:观察国产冻干非洲绿猴肾传代细胞(Vero细胞)为基质制备的狂犬病纯化疫苗临床应用的免疫效果和安全性。方法:选择门诊部就诊的犬致伤者240例,分为试验组和对照组。试验组接种冻干Vero细胞狂犬病纯化疫苗,对照组接种地鼠肾狂犬病纯化疫苗。2组人群均按照狂犬病疫苗暴露后常规免疫程序进行接种,于全程接种后15d测定中和抗体,并观察不良反应。结果:试验组抗体阳性率为96.7%,明显高于对照组的90.0%,P<0.05;不良反应发生率为10.8%,明显低于对照组的21.7%,P<0.05。结论:Vero细胞纯化疫苗抗体阳转率高、不良反应发生率低,临床应用优于地鼠肾纯化疫苗,适宜推广使用。     

人二倍体细胞和Vero细胞狂犬病疫苗暴露前使用的安全性和保护作用的比较研究

本研究目的是将新的Vero细胞狂犬病灭活疫苗(PVRV)的效力和对其的耐受力与人二倍体细胞狂犬病疫苗(HDCV)进行比较. 作者在一所兽医学校中,采用WHO推荐的暴露前接种程序,于0、7和21天对144名志愿者接种HDCV或PVRV.接种部位为上臂三角肌.疫苗为冻干制剂,效价至少为2.5IU/ml.在接种当天及接种1针后3、5周和4.5、15和21个月采血,用免疫荧光法检测抗体.     

吸附狂犬病疫苗：一种新的人用狂犬病疫苗

吸附狂犬病疫苗(RVA)是一种用于人类的新型细胞培养疫苗,于1988年3月18日获准使用。该疫苗是采用狂犬病病毒Kissling株适应于恒河猴胎肺二倍体细胞制成。用β丙内酯灭活病毒,并通过磷酸铝吸附浓缩。而磷酸铝还可作为一种佐剂。RVA使用的病毒株、细胞系和浓缩过程均不同于美国现有的人二倍体细胞狂犬病疫苗(HDCV)。由于RVA由磷酸铝吸附,所以是液体,而不是冻干制剂。 3000人在接触前和接触后接种以及加强接种后,有99%以上的人产生了满意的狂犬病中和抗体水平。推荐的RVA接种时间与     

弄清是否职务行为是违法主体认定的关键

案例:2007年4月,张某因被猫抓伤到甲卫生院就医.值班医生王某给其注射了1支人用狂犬病纯化疫苗,让张某带走2支,并收取了药费.后张某发现带走的人用狂犬病纯化疫苗瓶口松动,举报到我局.经查实上述人用狂犬病纯化疫苗是王某私自购进的,购进后存放于其办公桌内.经核查上述人用狂犬病纯化疫苗不是标示的生产企业生产的,属于假药.     

犬咬伤43763例免疫疗效

莆田县1955～1993年被犬咬伤者发生狂犬病185例,无一幸存,为掌握防治效果和对策,现将犬咬伤者注射人用狂犬疫苗和抗血清的疗效报告如下。1 免疫接种1.1 疫苗与抗血清来源 人用冻干狂犬疫苗(羊脑苗),系卫生部上海、长春、兰州生物厂出品;人用狂犬疫苗(细胞苗),系上海、长春、兰州、武汉、成都生     

高滴度水痘减毒活疫苗在健康幼儿中的效果

作者将来自日本的水痘病毒Oka株,在MRC-5人成纤维细胞上繁殖,收获感染细胞,浓缩,用稳定剂稀释,然后破坏细胞使之释放胞内的水痘-带状疱疹病毒(VZV),最后冻干,制成两批原始高滴度疫苗。将这两批疫苗于37℃放置10天,模拟长期贮存的老化过程,得到相应低滴度疫苗(热处理疫苗),安慰剂除无VZV外,制备方法与原始活疫苗相同。     

接种狂犬疫苗致急性变态反应1例

患者,女,22岁。2009年2月27日,在外地被狗咬伤。分别于当13,3月2日,3月6日在铁岭县防疫站接种人用狂犬病疫苗（Vero细胞）（注射剂,长春长生生物科技股份有限公司,批号不详）。于2009年3月13日在我院急诊室接种第4针：上臂三角肌注射冻干人用狂犬病疫苗（Vero细胞）（长春长生生物科技股份有限公司,批号：2007110205）。     

疫苗生产用细胞基质外源病毒检查的阳性对照病毒感染复数的筛选

目的 筛选阳性对照病毒在不同细胞基质中的最适感染复数（multiplicity of infection,MOI）,以优化水痘减毒活疫苗外源病毒因子检查法（细胞培养法）。方法 致细胞病变观察：将水痘-带状疱疹病毒以0.005、0.010、0.020的MOI分别接种至Vero、2BS和MRC-5细胞,培养7 d后观察细胞病变,病变较典型时对应的MOI即为最适MOI。血细胞吸附观察：将牛副流感病毒3型以0.1、0.2、0.4的MOI分别接种至Vero、2BS、MRC-5细胞,培养7 d后分别于2~8 ℃和20~25 ℃放置30 min,观察血细胞吸附,血细胞吸附较典型时对应的MOI即为最适MOI。结果 对Vero、2BS、MRC-5细胞,当水痘-带状疱疹病毒MOI分别为0.020、0.010、0.005时,30%~50%细胞出现典型病变;对Vero、2BS、MRC-5细胞,当牛副流感病毒3型MOI分别为0.1、0.2、0.4时,30%~50%细胞出现典型血细胞吸附。结论 水痘-带状疱疹病毒感染Vero、2BS和MRC-5细胞的最适MOI分别为0.020、0.010、0.005;牛副流感病毒3型感染Vero、2BS和MRC-5细胞的最适MOI分别为0.1、0.2、0.4。     

Immunogenicity of two modern tissue culture rabies vaccines in pre-exposure prophylaxis

Pre-exposure prophylaxis was given to employees supposed to be involved in rabies vaccine production in India. Prior to availability of the manufacturer's own human diploid cell (HDC) vaccine (Rabivax), immunization was executed with a chick embryo cell (CEC) vaccine (Rabipur). This constellation gave an opportunity to compare retrospectively immunogenicity of these two vaccines. The data was collected by retrospective analysis over more than three years at the clinic of Serum Institute of India Ltd. As per the standard protocol, persons with negative rabies vaccination history receive a dose of 1 ml of rabies vaccine intramuscularly on day 0, 7 and 28, and the virus anti-glycoprotein antibodies are measured one month after the third dose. The antibody levels > or =0.5 IU/ml are considered protective. The CEC and HDC vaccines were used during the analysis period. In all, 43 individuals received the CEC vaccine, 106 the HDC vaccine. The mean age of recipients was 33 years five months (Rabipur) and 30 years three months (Rabivax). All subjects in both groups were males. Five commercial batches of the CEC vaccine (129 doses) and seven batches of the HDC vaccine (318 doses) were used. Ninety-nine percent of the HDC and 93% of the CEC vaccine recipients were protected after the standard three dose schedule. Geometric mean titre was significantly greater for the HDC than CEC vaccine, being 5.05 IU/ml and 2.90 IU/ml, respectively (p = 0.0002). The HDC vaccine showed a good lot-to-lot consistency with respect to GMT both by ANOVA test and Nonparametric ANOVA test. On the other hand, the CEC vaccine demonstrated a variation in titres, when the lots were compared. Three out of four low-responders accepted a booster vaccination, and regardless of whether Rabipur or Rabivax was used, all three responded well one month after the booster. The Indian HDC vaccine compares well with the CEC vaccine in terms of immunogenicity. With HDC vaccines, cost has been an issue. However, since the new HDC vaccine has a comparable cost to the CEC vaccine, it may be possible to use it in large-scale vaccinations.     

叙利亚地鼠作为狂犬病暴露后免疫动物模型的研究

目的  对叙利亚地鼠（地鼠）作为狂犬病暴露后疫苗免疫效果动物模型的可行性进行研究。方法 将狂犬病病毒CVS株和CTN-1V株分别肌内感染不同周龄的地鼠和小鼠,观察动物对不同毒株的敏感性。用直接免疫荧光法检测CVS株进入地鼠脑组织的情况;用快速荧光灶抑制试验检测血清中和抗体。以不同病毒量CVS株感染8周龄雌性地鼠,确定暴露时病毒的最佳感染剂量。对暴露后地鼠用疫苗进行免疫,观察疫苗的保护效果。结果  地鼠感染后7 d左右出现狂犬病临床症状,同一病毒株对地鼠的致病力比小鼠强〔6.4～8.0 lg半数致死量（LD₅₀）/ml对3.4~6.5 lgLD₅₀/ml〕;3周龄和8周龄地鼠对病毒的敏感性无差异。感染后5~6 d病毒进入地鼠脑组织。以3.8～4.0 lg小鼠脑内半数致死量（MICLD₅₀）/ml的CVS株感染后6～7 d,地鼠血清中检出中和抗体。暴露后疫苗免疫结果显示,不同疫苗具有不同程度的保护效果。结论  地鼠对狂犬病病毒神经外途径感染敏感,临床症状典型,潜伏期恒定,感染后免疫血清抗体应答出现早,具备作为暴露后疫苗免疫动物模型的条件。     

冻干b型流感嗜血杆菌结合疫苗稳定性研究

目的 对以乳糖作为稳定剂的b型流感嗜血杆菌(Haemophilus influenzae type b,Hib)结合疫苗冻干剂型进行稳定性研究.方法 选取3批冻干Hib结合疫苗,分别于2～8℃保存42个月,20～25℃保存7个月,37℃保存5周.并于考察期内对疫苗进行外观检查、检测回收率(KD ＜0.2)、游离多糖含量...     

白细胞介素-2对狂犬疫苗细胞免疫应答增强作用的研究

为证实白细胞介素－2（IL－2）能否作为佐剂增强狂犬病毒灭活疫苗在小鼠体内的免疫应答，将CBA／J（H－2K）纯系鼠分为3组，分别注射IL－2＋狂犬病毒灭活疫苗、狂犬病毒灭活疫苗、生理盐水（正常对照）。结果表明，IL－2能够提高CBA／J（H－2k）纯系鼠对狂犬病毒灭活疫苗的免疫反应，加入IL－2后，小鼠体内NK细胞杀伤活性显著提高，达51，3±6．7％（P＜0．01），特异性细胞毒性T细胞（CTL）活性的二次反应达29．1±3．0％（P＜0.01）。     

Establishment of batch 4 of the Biological Reference Preparation (BRP) for rabies vaccine (inactivated) for veterinary use

9 laboratories from 7 countries including both laboratories from the public and private sector participated in a collaborative study organised under the aegis of the European Directorate for the Quality of Medicines Biological Standardisation Programme in order to establish batch 4 of the European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for rabies vaccine (inactivated) for veterinary use. Establishment of Ph. Eur. BRP batch 4 was necessary in order to replace Ph. Eur. BRP batch 3, the stocks of which were dwindling. 8 laboratories provided results. Ph. Eur. BRP batch 4 was calibrated against the 5th International Standard for inactivated rabies vaccine in International Units (IU) using the vaccination challenge method of the Ph. Eur. monograph 0451. The International Standard (IS), Ph. Eur. BRP batch 4 and batch 3 are all freeze-dried vaccines prepared by beta-propiolactone inactivation of the Pitman Moore strain of rabies. Based on the results of the study, a potency of 11 IU/vial was assigned to Ph. Eur. BRP batch 4 for rabies vaccine (inactivated) for veterinary use. Nevertheless, it was noted that the vaccination challenge assay used as the "golden standard" for potency determination of inactivated rabies vaccines for veterinary use is a crude assay requiring the use of a large number of animals. Evidence from this study and from the collaborative study to establish Ph. Eur. BRP batch 3 suggests that the assay is difficult to perform and provides highly variable results. The validation of a suitable in vitro alternative is therefore highly recommended, as is the possible improvement of the in vivo assay, which will most likely remain the "golden" standard.     

Immunogenicity and efficacy of Fermi-type nerve tissue rabies vaccine in mice and in humans undergoing post-exposure prophylaxis for rabies in Ethiopia

Rabies is an acute viral encephalitis that is invariably fatal following the manifestations of clinical signs. To subvert the course of the disease, rabies post-exposure prophylaxis (PEP) is widely utilized. The immunogenicity and efficacy of Fermi-type rabies vaccine produced in Ethiopia was determined in mice subjected to intracranial challenge with rabies virus, and in humans undergoing rabies PEP in Ethiopia. Mice were randomly assigned into 5 groups. Group 1 received 0.25 ml each of phenolized saline intraperitoneally for 14 consecutive days. Mice in groups 2-5 received 0.25 ml of rabies vaccine for human PEP for the same period of time. Blood samples were drawn from the retro-orbital vein of all mice on designated days for the determination of rabies virus neutralizing antibody (VNA) using the mouse serum neutralization test. Mice were subsequently challenged intracranially with rabies virus at a concentration of 64 MICLD50 90 days post initial vaccination. Rabies neutralizing antibody titers in the sera of immunized mice ranged from 4.6 to 25 IU/ml. Booster vaccine doses did not seem to induce significant increases in the immune response of vaccinated mice, all of whom withstood intracranial challenge with rabies virus. Rabies VNA was further determined in 12 patients vaccinated in accordance with the prescribed dosage of Fermi-type vaccine for human rabies PEP. Most had > 0.5 IU/ml of rabies VNA by day 14, and none detectable at day 1. In contrast to mice, booster doses of vaccine may contribute to slightly higher rabies VNA titers in humans but our small sample size, on top of significant defaulter rates in the study participants, limits our interpretation of the effects of booster vaccine doses. The results of this study are the first documentation of the efficacy and immunogenicity of the Ethiopian Fermi type nerve tissue vaccine in both humans and mice.     

手术治疗原发性食管小细胞癌疗效分析

目的分析手术治疗原发性食管小细胞癌的疗效。方法选择我院2004年8月至2006年6月26例行手术治疗的食管小细胞癌患者,所有患者均随访1～5年,对手术治疗后的效果,患者1、3、5年生存率进行观察。结果 26例食管小细胞癌患者后术后TNM分期Ⅰ期1、3、5年生存率分别为100%(6/6),66.67%(4/6),33.33%(2/6)。TNM分期Ⅱ期1、3、5年生存率分别为42.86%(6/14),7.14%(1/14),0(0/14)。TNM分期Ⅲ期生存率分别为33.33%(2/6),0(0/14),0(0/14)。患者死亡原因均为肿瘤转移至肝、肺等部位。结论原发性食管小细胞癌预后极差,外科手术是治疗I、Ⅱ期病例的主要治疗手段,术后化疗可提高疗效;对于Ⅲ、Ⅳ期病例,则应以化疗和放疗为主要治疗手段。     

Immunogenicity of rabies postexposure booster injections in subjects who had previously received intradermal preexposure vaccination

BACKGROUND: Preexposure rabies vaccination is recommended using the full dose intramuscular or less expensive reduced dose intradermal method. The reliability of the reduced dose intradermal preexposure regimen is still controversial. The objective of this study was to determine whether it will mount a predictable accelerated immune response after a simulated rabies exposure. METHOD: One hundred and thirty-eight veterinary students received intradermal or intramuscular preexposure vaccination using a potent batch of purified chick embryo rabies vaccine. They then received booster injections one year later. RESULTS: Subjects who received intradermal rabies preexposure vaccination, using 0.1 mL of a potent tissue culture vaccine on days 0, 7, and 28, had a lower postexposure booster antibody response 1 year later than subjects given the preexposure series intramuscularly. A significant number showed an unsatisfactory early anamnestic response. Residual neutralizing antibodies, 1 year after the intramuscular preexposure series, were also significantly higher in the intramuscular than in the 0.1 mL dose intradermal group. However, all study subjects had antibody titers above the minimum recommended level of 0.5 IU/mL by day 14. CONCLUSIONS: We conclude that not all subjects who received an intradermal preexposure vaccine series may be fully protected during the first 5 days after an exposure. Rabies immune globulin, injected into bite wounds and followed by a complete postexposure vaccine series, may be indicated if such a patient experiences a severe rabies exposure.