A randomised, double-blind, non-inferiority clinical trial on the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis (TdaP) vaccine in comparison to a tetanus and diphtheria (Td) vaccine when given as booster vaccinations to healthy adults

Background

Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults.

Purpose

To obtain clinical documentation of the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis combination vaccine (TdaP), when given as a booster vaccination to adults.

Methods

The trial was double-blind, controlled and randomised. 802 healthy adults, aged 18–55 years who had completed childhood vaccination with diphtheria, tetanus and whole cell pertussis vaccine (DTwP), were booster vaccinated with TdaP or Td. Blood samples were taken before and one month after the vaccination for serological analysis and adverse events were recorded during the one-month-follow-up period.

Results

The monocomponent acellular pertussis vaccine (aP) in the TdaP vaccine was immunogenic in adults with 92.0% of TdaP vaccinated subjects obtaining an anti-pertussis toxin (anti-PT) antibody booster response. TdaP was non-inferior to Td in eliciting seroprotective anti-tetanus and diphtheria antibody concentrations with more than 98% of subjects obtaining post-vaccination seroprotective concentrations (≥0.1 IU/mL). T and d booster response rates were 93.0% and 97.5%, respectively.The frequencies of solicited local adverse reactions were low and comparable between TdaP and Td vaccinees. In the TdaP group, 30.7% reported pain, 4.2% swelling and 2.0% erythema at the injection site. The most frequent solicited general symptoms were headache (20.4%), fatigue (17.0%) and myalgia (10.0%). In the Td group, 35.7% reported pain, 2.5% swelling and 3.2% erythema at the injection site, whereas headache, fatigue and myalgia were reported by 15.7%, 14.5% and 12.5%, respectively.In conclusion, TdaP Vaccine SSI was safe and immunogenic when given as a booster vaccination to adults. ClinicalTrials.gov registration number: NCT01033877.     

Immune response to tetanus booster in infants aged 15 months born prematurely with very low birth weight

Objectives

To compare humoral and cellular immune responses to tetanus booster vaccination in infants born prematurely with those born at full term and identify factors associated with the humoral response.

Methods

A prospective study was carried out on children born prematurely and with a birth weight <1500 g and with infants born at full term. At 15 months (pre-vaccination) and 18 months (post-vaccination), anti-tetanus antibodies were measured by ELISA; the intracellular interferon-gamma percentages of CD4+ T and CD8+ T cells after in vitro stimulation with tetanus toxoid were determined by flow cytometry. Chi-squared or Fisher's exact test was used to compare categorical variables. Student's t-test or Mann–Whitney test was used to compare numerical variables. Regression analysis was performed to determine factors associated with humoral immunity. Statistical significance was considered if p < 0.05.

Results

Sixty-four premature and 54 full-term infants were studied. The proportion of children immune against tetanus at 15 and 18 months was similar in both groups. The geometric mean of the antibodies was lower among the premature children at 15 months (p = 0.025) and was similar in both groups at 18 months (p = 0.852). The percentages of CD4+ and CD8+ T cells expressing intracellular IFN-γ were similar in both groups at 15 and 18 months. Gestational age <32 weeks was associated with a reduction of −0.116 IU/mL in the level of antibodies at 15 months. Breastfeeding >6 months was associated with a 3.5-fold greater chance of optimal protective (≥0.1 IU/mL) antibody level against tetanus at 15 months and an increase of 0.956 IU/mL in the level of antibodies at 18 months.

Conclusions

Humoral and cellular response following a tetanus booster was similar in both groups. Premature infants exhibited lower levels of anti-tetanus antibodies at 15 months of age, with the lowest levels in those born at a gestational age of less than 32 weeks. Breastfeeding was associated with greater levels of antibody against tetanus.     

宜昌市正常人群脊髓灰质炎、麻疹、白喉、破伤风抗体水平监测

1989年10月~1990年10月,对我市1444名正常人群进行了脊髓灰质炎、麻疹、白喉、破伤风抗体检测,结果表明:脊髓灰质炎抗体处于较高免疫力水平,I、II、III型抗体阳性率分别为95.00%、93.61%、94.71%,几何平均滴度(GMT)分别为103.57、94.61、83.80;白喉抗体处于中等免疫力水平(GMT=0.0829IU/ml);育龄妇女破伤风抗体处于低免疫力水平(GMT=0.0014IU/m1);母婴胎传麻疹抗体呈明显正相关(r=0.7153, P<0.0005)。本次调查为了解我市计划免疫人群的免疫水平及今后预防工作提供了可靠的科学依据。     

Dendritic shrinkage and dye-coupling between rat hippocampal CA1 pyramidal cells in the tetanus toxin model of epilepsy

A small dose of tetanus toxin injected into the rat hippocampus produces a chronic model of temporal lobe epilepsy. We have examined whether morphological changes occur in hippocampal CA1 pyramidal cells in this model by using intracellular injections of biocytin. Eight weeks after the injection of tetanus toxin, significantly more ‘dye-coupled’ cells were found in this group than in the buffer (control) injected group (63% compared with 7%). Half of these coupled cells appeared to be linked at the soma, and the other half by dendrodendritic contacts. Analysis of the dendritic trees revealed that the tetanus toxin group showed a decrease in complexity around the proximal to mid-apical dendritic regions and around the mid- to distal basal dendritic regions. The dye-coupling indicates that electrotonic interaction is induced or strengthened between hippocampal neurones, possibly as a result of the epilepsy-induced dendritic damage.     

海南省1997～2001年新生儿破伤风病例监测结果分析

目的 为了解海南省新生儿破伤风(NT)监测系统的运行情况及NT高发地区分布，以便调整下一步工作策略。方法 与急性驰缓性麻痹(AFP)病例监测系统同时运行开展NT监测，使用全国统一方法、标准进行病例个案调查和确诊，数据录入计算机进行统计分析。结果 1997-2001年全省各年监测报告发病率均远大于法定传染病报告系统或妇幼系统报告发病率，病例个案调查率逐步提高；已有6个消除NT项目市县实现了发病率降至1‰以下的目标，发病集中在陵水、昌江、东方等几个少数民族市县：567例病例，在家分娩占96.5％，母亲无破伤风类毒素(TT)免疫史占81．7％。结论 将NT监测纳入AFP专报系统同时运行是有效的，监测系统敏感性逐步提高，项目工作开展降低了NT发病率，部分市县实现了消除NT目标。影响NT发病的主要因素仍是不洁出生和育龄妇女没有TT接种     

A rapid and simple radioimmunological procedure for measuring low concentrations of tetanus antibodies

Summary A radioimmunological assay procedure allows the measurement of small amounts of tetanus antibodies; it should also be applicable to antibodies against other soluble antigens. It is based on the competition between dissolved and solid phase antibodies for labelled antigen. In the range of experimental error, the same antibody titers are found with the radioimmunological and with the mouse protection test. The detection limit is in the range of 0.001 IU/ml. The reaction conditions allow the determination of antibodies in multiple samples.     

大剂量安定为主治疗新生儿破伤风57例临床分析

目的:总结大剂量安定为主的治疗方案对新生儿破伤风的效果。方法:1998年至2003年收治的57例新生儿予以大量安定为主的治疗,安定的用法为:每次0.5 mg/kg-1 mg/kg静脉注射,每(1 h～2 h)/次,每次注射时间不少于3 min。抽搐好转后予以每次0.5 mg/kg-1 mg/kg的安定鼻饲,每(2 h～4 h)/次,然后根据患儿抽搐控制情况逐渐减少鼻饲安定量及延长鼻饲时间直至停药。结果:57例患儿中安定最大用量为每天15 mg/kg,最小用量为每天8mg/kg,单次最大剂量为1.5 mg/kg。治愈31例(54.4％);好转12例(21.1％);无效5例,其中3例应用肌松剂联合机械通气后治愈,2例需加用鲁米那或亚冬眠;放弃9例。治疗期间仅1例因呼吸抑制需行气管插管。结论:大剂量安定治疗破伤风经济,安全有效、副作用小,值得临床应用。