Tetanus incidence and immunity in Poland

The level of tetanus antibody was determined with the passive hemagglutination method in 503 sera of 10 to 90-year-old persons. Immunity to tetanus was age-dependent: the percentage of immune persons amounted to 90% –100% in persons below 40 years and then declined to 70% and 60% in persons in the 40 – 50 and above 50 year-old groups, respectively. Males above 30 years are better immunized than females. The comparison of the results of the present study with results of several periodic surveys performed in the last 27 years showed gradually increasing immunity level in all age groups. The findings are in agreement with age-dependent incidence of tetanus, which has become now, in Poland, a disease primarily of older people.     

履行项目承诺 促进“两纲”目标落实

“降低孕产妇死亡率和消除新生儿破伤风”项目 (“降消”项目 )实施一年半时间 ,初见成效。“降消”项目工作思路清晰 ,启动快 ,可操作性强 ,影响大 ,带动范围广 ,注重对供方的支持和对需方的救助。这个项目只剩半年时间 ,还存在一些困难和问题。因此 ,要增强实现项目目标的紧迫感 ,进一步加强领导 ;加大督查力度 ,及时解决项目实施中的困难与问题 ;深入进行技术培训和健康教育工作 ,发挥急救“绿色通道”的作用 ;巩固和发展项目成果 ,坚持不懈地抓好“降消”工作 ,带动农村的妇幼卫生工作。     

以聚合物微球为载体的破伤风类毒素蛋白疫苗免疫效果观察

目的 探索载破伤风类毒素（TT）蛋白的聚合物微球作为疫苗在动物体内的免疫效果。方法 采用溶剂蒸发技术制备包裹TT的聚乳酸及聚乳酸／聚乙醇酸共聚微球（PLGTTMS）,并以ELISA法和小鼠中和法测定免疫小鼠小鼠和豚鼠的血清中和抗体。结果 用这些载TT聚合物微球免疫豚鼠和小鼠后,所诱发的抗体反应大大高于未加佐剂的TT疫苗,且由大粒径和小粒径微球混和组成的PLATTMS所诱发的抗体反应呈现现明显的加强效应。用20LD50的破伤风毒素攻击后,氢氧化吸附的TT和包裹TT的不同聚合物微球免疫的小鼠均获得100％的保护率。结论 以聚乳酸及其与聚乙醇酸共聚微球为载体的破伤风类毒素蛋白疫苗在动物体内诱生的免疫反应显高于无佐剂疫苗,这为疫苗的开发提供了一条新途径。     

Tetanus immunization in pregnant women. Serum levels of antitetanus antibodies at time of delivery

The objective of this study was to determine the tetanus immunity status of pregnant women at the time of delivery according to tetanus toxoid (TT) vaccination coverage during their most pregnancy. The serum anti-tetanus antibody levels of 493 mothers who had live births at a hospital in Ankara were determined by enzyme-linked immunosorbent assay (ELISA). Protected women were defined as those with serum antibody levels 0.6 IU/ml. Overall, 69.0% of mothers had protective tetanus antibody titers at the time of delivery. The rates of protection for mothers who had received no vaccination, one TT dose, or two TT doses during pregnancy were 46.4, 93.5, and 95.6%, respectively. Vaccinating every pregnant woman with at least one dose of TT would be an affordable and effective way to protect against neonatal tetanus, and would be a step toward eliminating the deaths that continue to occur due to this preventable disease in Turkey.     

深圳市2001～2005年新生儿破伤风流行病学分析及干预措施

目的:了解深圳市新生儿破伤风的流行病学特征,为控制和消除新生儿破伤风提供科学依据。方法:用描述流行病学方法,对2001～2005年深圳市妇幼信息系统监测的资料进行统计学分析。结果:深圳市2001～2005年新生儿破伤风的发病率在0.42‰～2.07‰之间,死亡率在0.03‰～0.36‰之间,两率均呈明显的下降趋势,2001年全市6区中有5个区报告新生儿破伤风,2005年仅有3个区报告新生儿破伤风,2001年新生儿破伤风发生率>1‰的有宝安区、龙岗区,2005年新生儿破伤风发生率>1‰的区数已下降为零。宝安区和龙岗区合计占全市总例数的88.35%。流动人口新生儿破伤风发病率高于户籍加暂住人口新生儿破伤风发病率。352例新生儿破伤风均为院外分娩,新生儿破伤风的母亲均未接种破伤风类毒素。结论:新生儿破伤风多发生于流动人口中。不安全接生是新生儿破伤风发病的主要原因。采取综合干预措施可以控制新生儿破伤风的发病,提倡和推广住院分娩,是目前消除新生儿破伤风的主要措施。     

Limited proteolysis of single-chain tetanus toxin by tissue enzymes,in cultured brain tissue and during retrograde axonal to the spinal cord

Summary Single-chain toxin was investigated in vitro and in vivo for limited proteolysis into the fully active two-chain toxin. Plasmin from serum, elastase and gelatinase from leucocytes, as well as clostripain from C. histolyticum cleaved single-chain toxin and increased by that way its ability to inhibit [³H]noradrenaline release in vitro. Cultured mouse brain generated fragments from ¹²⁵I-single-chain toxin which were cell-associated. Some of them comigrated in electrophoresis with light and heavy chain after mercaptolysis. When injected i. v. into rats, ¹²⁵I-single-chain-toxin disappeared from the blood with a half-life of about 11 h without signs of nicking. However, after its injection into the triceps surae muscle both single- and two-chain toxin were found in the ipsilateral ventral horn of the spinal cord. Thus single-chain toxin is subjected to limited proteolysis by enzymes involved in tissue damage, by cultured brain tissue, and during or after its retrograde axonal transport to the spinal cord. Limited proteolysis is necessary for the release of the light chain known to mediate the action of toxin on several systems.     

Improved Immunogenicity of Tetanus Toxoid by Brucella abortus S19 LPS Adjuvant

Background: Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella abortus LPS is less toxic and has no pyrogenic properties compared to LPS from other gram negative bacteria. Objectives: To evaluate the adjuvant effect of B. abortus (vaccine strain, S19) LPS for tetanus toxoid antigen (TT) and to investigate the protective effect of different tetanus vaccine preparations. Methods: LPS was extracted and purified from B. abortus S19 and KDO, glycan, phosphate content, and protein contamination were measured. Adipic acid dihydrazide (ADH) was used as a linker for the conjugation of TT to LPS. Different amounts of B. abortus LPS, TT, TT conjugated with LPS, and TT mixed with LPS or complete Freund’s adjuvant (CFA) were injected into mice and antibody production against TT was measured. The protective effect of induced antibodies was determined by LD50. Results: Immunization of mice with TT+LPS produced the highest anti-TT antibody titer in comparison to the group immunized with TT without any adjuvant or the groups immunized with TT-LPS or TT+CFA. Tetanus toxid-S19 LPS also produced a 100% protective effect against TT in immunized mice. Conclusion: These data indicate that B. abortus LPS enhances the immune responses to TT and suggest the possible use of B. abortus LPS as an adjuvant in vaccine preparations.     

Intrathecal tetanus immunoglobulins in the management of tetanus

Objective To study the clinical profile, treatment and outcome of tetanus in children treated with intrathecal tetanus immunoglobulin. (TIG) Methods Retrospective analysis of hospital records of tetaus cases admitted to the pediatric ICU during the five year period between 1999 to 2004 was done. Results There were 66 cases of tetanus treated with intrathecal TIG. Children below 5 years formed 53% of cases and 47% were above 5 years. Totally unimmunized children constituted 82% of cases and 18% partially immunized children. The portal of entry was otogenic in 58% of cases and injury in 30% of cases. The common complications observed included thrombophlebitis, aspiration pneumonia, laryngospasm and autonomic system involvement. There were no complications specific to intrathecal administration of TIG. The mortality due to tetanus was 9%. Discussion Mortality and morbidity due to tetanus was less in the present study compared to other centers where TIG is given intramuscularly. Conclusion Intrathecal TIG is effective in the treatment of mild and moderate tetanus. Randomized controlled clinical trials are needed to evaluate the efficacy of intrathecal TIG in the management of severe tetanus.     

Distinct sites of action of clostridial neurotoxins revealed by double-poisoning of mouse motor nerve terminals

(1) We investigated the effects of single- and double-poisoning with tetanus toxin (TeTx), botulinum neurotoxin type A (BoTx A) and botulinum neurotoxin type B (BoTx B) on spontaneous and nerve-evoked quantal transmitter release at motor endplates of the triangularis sterni preparation of the mouse. (2) Inhibitory effects of TeTx and BoTx B on spontaneous and nerve-evoked transmitter release were very similar, except that the action of BoTx B required 500-fold lower concentrations and was less dependent on temperature. BoTx A caused stronger inhibition of quantal release than TeTx or BoTx B, but was comparatively much easier counteracted by 4-aminopyridine (4-AP). (3) In contrast to BoTx A, with TeTx or BoTx B the increase of transmitter release following onset of 50 Hz nerve stimulation was delayed for a few seconds and synaptic latencies of quanta showed large variations. This release pattern was also evident in all double-poisoning experiments, regardless of intoxication sequence. (4) Inhibition of evoked release was found to be slightly stronger with TeTx than with BoTx B, so the amount of nerve-evoked quanta released after double-poisoning with any sequence of these toxins always approached that of TeTx. In no case supraadditive actions were observed. (5) A strong reduction of evoked quanta was observed when BoTx A was applied in addition to either of the two other toxins. With reversed poisoning sequences (BoTx A-TeTx or BoTx A-BoTx B) the resulting values remained at the extremely low level of BoTx A. (6) In the presence of 4-AP double-poisoning with any combination between BoTx A and TeTx or BoTx B (regardless of intoxication sequence) revealed supra-additive effects, since the number of quanta released was considerably lower than that obtained with any of the toxins alone (in the presence of 4-AP). (7) Our results indicate that tetanus toxin and botulinum toxin type B have a common site of action which is different and independent from that of botulinum toxin type A.This is part of the thesis of M. G. to be presented to the Fachbereich Humanmedizin, Justus-Liebig-Universität Gießen