Characterization of the tetanus toxin model of refractory focal neocortical epilepsy in the rat

PURPOSE: To characterize in detail a model of focal neocortical epilepsy. METHODS: Chronic focal epilepsy was induced by injecting 25-50 ng of tetanus toxin or vehicle alone (controls) into the motor neocortex of rats. EEG activity was recorded from electrodes implanted at the injection site, along with facial muscle electromyographic (EMG) activity and behavioral monitoring intermittently for up to 5 months in some animals. Drug responsiveness was assessed by using the antiepileptic drugs (AEDs) diazepam (DZP) and phenytoin (PHT) delivered systemically, while 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), a competitive antagonist at AMPA receptors, was administered directly to the brain to investigate the potential benefits of focal drug delivery. RESULTS: Tetanus toxin induced mild behavioral seizures that persisted indefinitely in all animals. EEG spiking activity, occurring up to 80% of the time, correlated with clinical seizures consisting of interrupted behavioral activity, rhythmic bilateral facial twitching, and periods of abrupt motor arrest. Seizures were refractory to systemic administration of DZP and PHT. However, focal delivery of NBQX to the seizure site reversibly reduced EEG and behavioral seizure activity without detectable side effects. CONCLUSIONS: This study provides a long-term detailed characterisation of the tetanus toxin model. Spontaneous, almost continuous, well-tolerated seizures occur and persist, resembling those seen in neocortical epilepsy, including cortical myoclonus and epilepsia partialis continua. The seizures appear to be similarly resistant to conventional AEDs. The consistency, frequency, and clinical similarity of the seizures to refractory epilepsy in humans make this an ideal model for investigation of both mechanisms of seizure activity and new therapeutic approaches.     

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.     

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。     

内蒙古自治区消除新生儿破伤风项目工作评价

目的落实卫生部和澳大利亚政府国际发展局援助内蒙古自治区开展消除新生儿破伤风(NT)项目,评价乌拉特中旗、乌拉特后旗、乌审旗、鄂托克前旗NT高危旗所有18~35岁的育龄期妇女开展破伤风疫苗(TV)接种效果。方法按照0、1、7个月程序开展突击接种3剂TV,每剂次0.5ml。结果4个旗应种35 138人,报告接种率TV192.79%,TV291.43%,TV390.30%,12个项目旗2003~2005年无NT病例报告。结论应在保证清洁接生的基础上,对NT高危旗育龄期妇女开展TV常规免疫接种,加强NT监测。     

Attendance and vaccination at immunization clinics in rural Gambia before and during the COVID-19 pandemic

IntroductionThe COVID-19 pandemic has affected the delivery of essential health services, such as routine immunization. We assessed the impact of the pandemic on the uptake of routine immunization in rural Gambia.MethodsWe collected real-time vaccine administration data in the Basse and Fuladu West Health & Demographic Surveillance Systems from September 01, 2019, to December 31, 2020. We assessed the monthly number of Expanded Program on Immunization (EPI) clinic attendances and vaccines administered, comparing data during the baseline period (September 01, 2019–March 31, 2020), COVID-19 interruption period (April 01–June 30, 2020), initial recovery period (Jul 01–September 30, 2020) and the late recovery period (October 01–December 31, 2020).ResultsCompared to the baseline period, there was an overall average monthly decline of 13.4% in EPI attendance and 38.3% reduction in average monthly immunizations during the interruption period. This decrease was particularly noticeable for Bacille Calmette-Guérin (BCG) (47.2%), birth dose hepatitis B (Hep B) (46.9%), 1st dose pentavalent (Penta1) (43.1%), 1st dose pneumococcal conjugate vaccine (PCV1) (42.4%), and measles vaccines (15.5%). Comparing the late recovery to baseline period, average monthly EPI attendance was 5.3% higher, with 1.9% increase in average monthly immunizations. Monthly immunizations for BCG were 3.0% greater, 2.5% greater for Hep B, 22.7% greater for oral polio vaccine (OPV1), 2.0% less for Penta1, 19.2% less for Penta2, and 2.6% less for PCV1.ConclusionThe reduced EPI attendance during the pandemic interruption period lasted only 3 months. Significant recovery in EPI attendance occurred during the late recovery period, while rates of monthly immunization returned to pre-pandemic levels for most antigens. EPI programmes should implement strategies to deliver missed antigens when infants do present to EPI clinics, aware that missed doses may be age dependent.     

Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14–15 years

Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark).Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20 μg) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5 μg).The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children.Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence.The adolescent study was registered at ClinicalTrials.gov on 26 March 2009 (NCT00870350).     

Analysis of tetanus toxin peptide/DR recognition by human T cell receptors reconstituted into a murine T cell hybridoma

We have previously reported that human T cell receptors (TcR) selected in the class II-restricted (HLA-DRB1*1302) response to a tetanus toxin peptide (tt830-843) frequently used the Vβ2 germ-line segment which paired with several Vα segments and that the putative CDR3 of both α and β chains showed remarkable heterogeneity. To analyze the structural basis for recognition of the tt830-843/DR complex, five of these TcR were reconstituted into a murine T cell hybridoma, 58 α^?β^?, by expressing the human α and β variable regions joined to the mouse α and β constant regions, respectively. The chimeric TcR, expressing the same Vβ germ-line segment (Vβ2), two expressing Vα21.1, twoVα17.1 and one Vα8.1 were shown to have the expected antigen specificity and DR restriction. Two lines of evidence suggested that the putative CDR3, although not conserved in these TcR, played a key role in recognition. First, two TcR with identical V germ-line segments but distinct CDR3 showed large differences in their capacity to react with the ligand. Second, interchanging the α and β chains from tt830-843/DR1302-specific TcR which differed in their CDR3 sequences invariably led to loss of recognition. We also asked whether germ-line Vα17.1 could functionally replace Vα21.1, as they appear to be related in their primary sequence. However, as in the case of CDR3 exchanges, Vα replacement abrogated TcR reactivity. Taken together, these data underline the fine interdependence of the structural components of the TcR binding site in defining a given specificity. Four of the TcR studied displaying promiscuous recognition were also tested against different DR alleles and site-directed mutants. The results of these experiments suggested that, in spite of their structural heterogeneity, anti-tt830-843 TcR may have a similar orientation with respect to the peptide/DR complex. The reconstitution system described herein should represent a valuable tool for detailed studies of human TcR specificity.     

Year of birth,sex and residence,as ≪ determinants ≫ of tetanus incidence and immunity in Italy

Regional results of a seroepidemiological study and official notification data are evaluated to describe the situation of tetanus in Italy. Tetanus incidence has been decreasing during the past years. Vaccination has been the principal means of tetanus prevention. Trend analyses for sex- and age-specific rates suggest a change of exposure, presumably linked to the transformation of the Italian society after the World War II, a higher incidence among the elderly as a function of poor coverage and vanishing immunity. Regional data show remarkable variability in prevalence of susceptible population. Reported rates by region are different. Different degrees of regional underreporting in case notification is suggested.     

Pancuronium blood level monitoring in patients with tetanus

Overdosage of muscle relaxant has been given as a possible explanation for the hypotensive episodes occurring during the management of tetanus. The aim of the present work was to study the pharmacokinetics of pancuronium during long term infusion. Pancuronium was administered to eight patients with severe tetanus for a period varying from 8 to 24 days. The concentration of pancuronium was measured daily in plasma and urine using a fluorimetric method. The plasma concentration varied from 0.27 to 0.48 g/ml. No tendency to accumulation was observed. The plasma concentration fell rapidly below the level associated with muscle relaxation when pancuronium was discontinued. This absence of accumulation can be explained by a rapid elimination of pancuronium through the kidney according to a process of ultrafiltration.This work was supported by grants from Faculté de Médecine Xavier-Bichat (Université Paris VII). This work was presented in part at the Second World Congress on Intensive Care, September 1977, Paris, France     

Evaluation of left ventricular performance during sympathetic nervous storm in a case with severe tetanus by transesophageal M-mode echocardiography

Transesophageal M-mode echocardiography was applied for the evaluation of left ventricular performance in a case of severe tetanus with labile hypertension due to sympathetic nervous ‘torm’. When systemic blood pressure was elevated, increases in pulmonary arterial pressure, cardiac output, left ventricular enddiastolic diameter, fractional shortening and mean velocity of circumferential fiber shortening were noted. No changes were found in total peripheral vascular resistance or left ventricular endsystolic diameter. Positive pressure ventilation, rendered standard transthoracic echocardiography ineffective.