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PubMed1979

[Local reactions after repeated tetanus vaccinations].

Subjects who had exhibited a strong local reaction after vaccination with tetanus toxoid showed a high serum antitoxin titer. This observation confirms earlier findings published in the United States. Since the falloff rate in tetanus antitoxin, year by year, is no more than 30%, such patients should not receive a new booster injection in the following 10 years unless the risk of tetanus is considered great. When boostering these persons, the dose of tetanus toxoid can be reduced to 1-2 Lf.

Adult↗

PubMed1966

The use of toxoid for the prevention of tetanus neonatorum. Final report of a double-blind controlled field trial.

With a view to determining the effectiveness of a method for the control of tetanus neonatorum which would be independent of medical examination or care, a double-blind field trial covering 1618 women was conducted between 1961 and 1966 in a rural area of Colombia with an estimated existing tetanus neonatorum death rate of 11.6 per 100 births. The study group was given 1-3 injections of 1 ml of an aluminium-phosphate-adsorbed tetanus toxoid more than 6 weeks apart, and the control group a similar number of injections of an influenza-virus vaccine.There was no statistically significant difference between those in the two groups given one injection. Those in the control group given 2 or 3 injections had a tetanus neonatorum death rate of 7.8 deaths per 100 births, and the corresponding subjects in the study group had none. This difference is unlikely to have occurred by chance.

Adolescent↗

PubMed1979

Immunity to tetanus and diphtheria in various age groups of the Polish population.

The concentration of tetanus and diphtheria antitoxins was determined in 279 sera of 18 to 81-year-old women and 509 sera of 22 to 46-year-old men. Tetanus antitoxin content was determined also in 246 samples of fluid from human placentas and 428 lots of commercial human normal immunoglobulins. Immunity to tetanus was clearly age-dependent: in younger age groups the percentage of immunized persons amounted to 90%-100%, in middle-age groups to about 80%, and at age above 60 to about 25%. The findings are in agreement with age-dependent incidence of tetanus, which has become now in Poland a disease primarily of older people. Two groups of the population are now protected against diphtheria: a younger group under 20, and an older one above 40. Immunity in younger age groups was induced by artificial immunization, and among older persons by natural immunization through contact with diphtheria bacilli during severe diphtheria epidemics in the past. Between these groups, gaps exist including 20-30 years of age, who are sensitive to diphtheria.

Adolescent↗

PubMed1984

[Immunity to diphtheria and tetanus in some of the administrative territories of the RSFSR].

The article deals with the state of immunity to diphtheria and tetanus among the adult population in some administrative regions of the RSFSR. Of the children and adults covered by the survey, 91.3-96.7% were found to have protective antibody titers against diphtheria and 98.7-100%, against tetanus. An essential drop in the level of immunity to diphtheria in persons over 18 years of age was revealed: 71.7% of them were nonimmune, which correlated with the high morbidity rate among these persons. At the same time the percentage of adults nonimmune to tetanus was considerably lower than that of adults nonimmune to diphtheria, reaching only 27.1%. The state of immunity to tetanus in adults was found to depend on the seasons.

Adolescent↗

PubMed1995

[Tetanus vaccination. Evaluation of a program of health promotion in a family medicine unit].

OBJECTIVE: To assess the effectiveness of a tetanus immunization poster at a medical clinic in encouraging patients to request immunization against tetanus with d2T5. DESIGN: Quasi-experimental study. SETTING: The Family Medicine Unit (F.M.U.) at the Centre hospitalier de l'Université Laval (C.H.U.L.), a tertiary hospital in the region of Quebec City. PARTICIPANTS: All patients over 7 years of age at CHUL's FMU between February 22 and March 19, 1993. INTERVENTIONS: Poster promoting tetanus immunization displayed in waiting room during test weeks 2 and 4 and withdrawn during control weeks 1 and 3. MAIN OUTCOME MEASURE: Proportion of patients vaccinated with d2T5. RESULTS: The proportion of patients vaccinated during the test weeks was the same as the proportion vaccinated during the control weeks. Week 1: 1/507 (0.20); Week 2: 1/394 (0.25); Week 3: 1/441 (0.23); Week 4: 1/486 (0.21). CONCLUSION: The presence of the posters in the waiting room had no impact on tetanus immunization at CHUL's FMU.

Adolescent↗

PubMed1993

[A study on risk factors and control of neonatal tetanus during 1975-1990 in Yichang City].

Retrospective survey on the mortality of 21 cases of neonatal tetanus during 1975-1990 and their case-control study on death risk factors were reported in Yichang City. Surveillance and control of neonatal tetanus were emphasized on suburbs. Serological survey of tetanus antibody in women aged 15 to 40 and mothers and their newborn babies were carried out. The protective rate was 3.75% (GMT = 0.0014 IU/ml). The result showed that tetanus antibody in the women of childbearing age was at the lowest level. There was a significant positive correlation through vertical transmission between mothers and their newborn babies (r = 0.7096, P < 0.0005). And the successful immunization in 65 pairs of children was 100%. It was suggested that we should consolidate EPI and promote maternal and child health plan and a primary-health-care program in Yichang City.

Adolescent↗

PubMed1993

Epidemiological factors associated with neonatal tetanus mortality: observations from a cluster survey in Nigeria.

A cluster survey on neonatal tetanus (NNT) mortality was conducted in Kano Metropolis, Northern Nigeria, to investigate epidemiological factors associated with NNT mortality. The survey was a two-stage cluster sampling technique and lasted for two weeks. A total of 2,623 live-births were recorded over a 12-month period. Less than 40% of the births followed two or more antenatal visits and tetanus toxoid coverage was 32.0%. Over 60% of births were outside hospitals and related facilities. Of the epidemiological factors investigated, only antenatal care, tetanus toxoid coverage, hospital delivery, poor cord management and traditional surgery showed significant association with NNT death. It is suggested that an appropriate community-specific prevention strategy for the region should include health education to improve utilisation of antenatal and hospital-delivery facilities, discourage traditional surgery and improve tetanus toxoid coverage. A case is also made for training and involvement of traditional birth attendants (TBAs) since most deliveries occurred outside hospitals and related facilities.

Cluster Analysis↗

PubMed1993

The foetal immune response to maternal tetanus toxoid immunization.

Paired maternal and cord blood samples were collected at delivery from 150 women who received varying doses of tetanus toxoid during pregnancy. Tetanus specific IgM and IgG antibodies were measured in them by standard ELISA with a sensitivity for IgM of 0.001 mg/ml, and for IgG of 0.0003 IU/ml. In 22 infants an additional estimation of tetanus antibody was made 1 month after birth. The presence of specific IgM in 78% of cord samples established an active foetal immune response. The titre did not alter significantly with the number of TT doses given to the mother. Foetal IgM rose in 60% of cases at one month of age compared to cord blood levels. At this time IgG levels were uniformly diminished in accord with a maternally derived passively transferred antibody. No switch of foetal IgM to IgG production was evident. The foetal immune response thus did not confer active protection against tetanus.

Adolescent↗

PubMed1993

A single dose vaccine to prevent neonatal tetanus.

Neonatal tetanus kills 2,00,000 infants annually in India. To simplify the logistics of tetanus immunization in pregnancy a potent single dose vaccine containing 250 Lf tetanus toxoid (TT) was developed. When administered to 200 unimmunized primigravidae in the last trimester of pregnancy, all generated protective titres of tetanus antitoxin (> or = 0.01 IU/ml) at delivery as measured by the mouse neutralization method. All 125 hospital born infants of these mothers had antitoxin 0.01 IU/ml in cord blood. Protective levels of antitoxin persisted in 38 babies who followed up at 3 months and in 25 more seen between 4 and > or = 6 months;--none had received infant immunization. No adverse effects of 250 Lf (TT) were encountered in the mothers and there was no increase in stillbirths. The vaccine appears suitable for mass immunization.

Antibodies, Bacterial↗

PubMed2000

Blink reflexes and the silent period in tetanus.

Abnormalities of the silent period (SP) and blink reflexes occur in diseases that interfere with inhibitory pathways, such as tetanus and stiff-person syndrome (SPS). The SP is abnormal in tetanus but not in SPS. Studies of the blink reflex in tetanus are limited. In this report, a patient with generalized tetanus is described. The masseteric-and mixed-nerve SP was absent or truncated. In contrast to SPS, blink reflex studies revealed no bilateral R1 component, and a discrete R3 was only present ipsilateral to right supraorbital stimulation. This reflects the distinct inhibitory pathways underlying these disorders.

Adult↗

PubMed1979

Muscle and serum adenosine triphosphatase in patients suffering from tetanus.

Serial estimation of muscle and serum adenosine triphosphatase (ATPase) activity was performed in 16 healthy control patients and 32 cases with tetanus. There was no significant difference due to age and sex in muscle and serum ATPase activity between the normal and tetanus cases. Tetanus patients showed a marked increase in muscle and serum ATPase activity as compared to normal. The ATPase activity increased with the severity of convulsion and disease. There was increased mortality in tetanus patients having higher values of muscle and serum ATPase.

Adenosine Triphosphatases↗

PubMed1988

Tetanus toxin binding to isolated and cultured rat retinal glial cells.

The presence of immunocytochemically detectable membrane receptors for tetanus toxin, supposedly composed of higher gangliosides, is widely accepted as a marker of neuronal cells. We now demonstrate that Müller cells, a unique glial cell type of the vertebrate retina, possess specific tetanus toxin (TT)-binding sites. Single cell suspensions were prepared from adult rat retina by a gentle dissociation method, and the Müller cells, unequivocally identified by their morphology, could be immunocytochemically double-labeled by antisera to vimentin and to TT. The expression of complex gangliosides by identified Müller cells was also demonstrated by immunofluorescence labeling with the monoclonal antibody A2B5. Using the double-immunolabeling method for the identification of Müller cells we show that specific tetanus toxin binding is acquired by these cells during postnatal maturation both in vivo and in vitro. In vivo the percentage of tetanus toxin-positive Müller cells increases from 0% in 4-day-old animals to 10% on postnatal day 8, reaching the adult level of about 95-100% around day 30. In retinal monolayer cultures prepared from newborn rats, the majority (65%) of vimentin-positive non-neuronal cells became TT-positive during a 2-week culture period, indicating that this population of non-neuronal cells represents differentiating Müller cells. Again, comparable results were obtained with A2B5, supporting the conclusion that Müllerian glia expresses surface molecules, which are normally regarded as neuronal markers.

Age Factors↗

PubMed1993

Tetanus toxin light chain expression in Sertoli cells of transgenic mice causes alterations of the actin cytoskeleton and disrupts spermatogenesis.

Tetanus toxin is a powerful neurotoxin known to inhibit neurotransmitter release. The tetanus toxin light chain is a metalloprotease that cleaves some members of the synaptobrevin gene family with high specificity. Here, we report the expression of a synthetic gene encoding the tetanus toxin light chain in the seminiferous epithelium of transgenic mice. Spermatogenesis was severely impaired and mature spermatozoa were completely absent. Late spermatids exhibited pleomorphic shapes and acrosomal distortions. The number of Leydig cells was greatly increased. In situ hybridization analysis revealed that the toxin acts on Sertoli cells. Affected cells exhibited an aberrant distribution of actin filaments and many cells contained large vacuoles. Our results demonstrate that tetanus toxin is active in non-neuronal cells and suggest an important function for members of the synaptobrevin gene family during the late stages of spermatogenesis.

Actins↗

PubMed2006

Immunization does not interfere with uptake and transport by motor neurons of the binding fragment of tetanus toxin.

The nontoxic binding domain of tetanus toxin (fragment C or TTC) readily undergoes retrograde axonal transport from an intramuscular injection site. This property has led to investigation of TTC as a possible vector for delivering therapeutic proteins to motor neurons. However, the vast majority of individuals in the developed world have been vaccinated with tetanus toxoid and have circulating antitetanus antibodies that cross-react with TTC and may block the delivery of a TTC-linked therapeutic protein. However, it is uncertain whether the immune response is capable of completely neutralizing an intramuscular depot of protein prior to its internalization by presynaptic nerve terminals, where it is inaccessible to antibody. We have evaluated uptake of rhodamine-labeled TTC following intramuscular injection in normal animals and animals vaccinated with tetanus toxoid prior to injection of fluorescently labeled TTC. All animals demonstrated uptake of TTC, with fluorescence appropriately localized to the hypoglossal nerve and nucleus. The distribution and intensity of fluorescence within neurons and processes were indistinguishable between the two groups and were characteristic of TTC. Vaccinated animals showed levels of uptake of TTC into the brain comparable to those of immunologically naïve animals as measured by quantitative fluorimetry. All vaccinated animals had protective levels of antitetanus antibodies as measured by ELISA. Uptake of TTC by nerve terminals from an intramuscular depot is an avid and rapid process and is not blocked by vaccination associated with protection from tetanus toxin.

Animals↗

PubMed1994

Interlaboratory validation of in vitro serological assay systems to assess the potency of tetanus toxoid in vaccines for veterinary use.

An interlaboratory validation study was carried out in seven laboratories to evaluate the suitability of in vitro serological assay systems for the assessment of the potency of tetanus toxoid in single and multicomponent vaccines for veterinary use. Nine commercial vaccines and one experimental tetanus toxoid preparation were selected for immunization purposes according to Method A of the European Pharmacopoeia. Levels of tetanus antibodies in guinea-pig and rabbit serum samples were estimated by indirect ELISA, toxin binding inhibition (ToBI) test, passive haemagglutination (HA) test and by the prescribed standard toxin neutralization (TN) test in mice. Estimates of potency obtained by in vitro tests and by TN test were in good agreement for the various vaccines tested and for antibody levels of individual serum samples in the range 2.6 IU/ml to 266 IU/ml. Significant (P < 0.05) intralaboratory variation occurred less frequently for ELISA and ToBI test than for HA test. The frequency of significant (P < 0.05) interlaboratory variation was acceptable for the ELISA and the ToBI test but greater variation was observed for the HA test. It is concluded that the ELISA and ToBI tests are suitable in vitro assay systems for assessing the potency of tetanus toxoid in batches of single and multicomponent vaccines for veterinary use. Rigid standardization of the HA test is essential before this test can be used for the same quality control purpose.

Animals↗

PubMed2002

Calibration of replacement international standard and European pharmacopoeia biological reference preparation for tetanus toxoid, adsorbed.

Here we report the characterisation of a preparation of tetanus toxoid, adsorbed, and its calibration by 27 laboratories in 19 countries in a joint international collaborative study co-sponsored by World Health Organization (WHO) Expert Committee of Biological Standardization (ECBS) and the European Biological Standardisation Programme of European Directorate for the Quality of Medicines (EDQM), Council of Europe. Calibration was in terms of the Second International Standard (I.S.) for Tetanus Toxoid, Adsorbed, by the established WHO/European Pharmacopoeia (Ph Eur) challenge methods. The replacement standard preparation was found to have a unitage of 469 IU/ampoule on the basis of its calibration in guinea-pigs and 496 IU/ampoule on the basis of its calibration in mice. Assessment, both within the collaborative study and as part of candidate characterisation, indicated satisfactory stability of the candidate preparation. This study also provided some information on the effect of mouse strain on potency testing of tetanus vaccines. A limited assessment of the impact of the replacement standard on testing of current production batches of vaccines was also carried out by four manufacturers. This study did not directly address the serological approaches to potency testing. However, one laboratory offered data from mouse serology assay, which gave comparable estimates to in vivo mouse bioassay. Based on the results of this study and with the agreement of participants, the candidate standard was established as the Third International Standard for Tetanus Toxoid, Adsorbed (coded 98/552) by the WHO Expert Committee of Biological Standardization (ECBS) in November 2000. The same preparation was also established as the second Ph Eur Biological Reference Preparation (Ph Eur BRP, batch no. 2) by the Steering Committee of the Biological Standardisation Programme of the EDQM and approved by the European Pharmacopoeia Commission.

Animals↗

PubMed1990

Establishment of stable mouse/human-human hybrid cell lines producing large amounts of anti-tetanus human monoclonal antibodies with high neutralizing activity.

To establish stable hybrid cell lines producing human anti-tetanus antibody with high toxin-neutralizing activity, peripheral lymphocytes from humans hyperimmunized with tetanus toxoid were, after in vitro antigen stimulation, fused with a mouse/human heteromyeloma or human lymphoblastoid cell line and cloned. Unlike the IgM secretors (six clones), the IgG secretors we obtained (six clones) produced anti-tetanus human monoclonal antibodies with high neutralizing activity (the highest one, cell line G2, 4.3 IU/100 micrograms IgG). Appropriate combinations of three or four kinds of monoclonal antibodies of the IgG type resulted in markedly increased neutralizing activity comparable with that of anti-tetanus human polyclonal immunoglobulin preparations currently used clinically on the basis of toxin-specific IgG content. Five of these cell lines produced 10-20 micrograms of antibody per ml for more than 3 months. The cell line G2 produced 6 mg of antibody per day in serum-free medium in a 500-ml bioreactor in perfusion culture and 13-104 mg in a nude mouse. These cell lines satisfied, for the first time, the minimal requirements for applying human monoclonal antibodies to clinical use.

Animals↗

PubMed1992

Evidence for a link between specific proteolysis and inhibition of [3H]-noradrenaline release by the light chain of tetanus toxin.

The light chain of tetanus toxin is known to inhibit the Ca(2+)-evoked release of [3H]-noradrenaline from digitonin-permeabilized bovine adrenomedullary cells in culture but does not change the basal outflow or the total cellular radioactivity. Evidence for the involvement of proteolysis in this effect was obtained by three approaches. First, the permeabilized cells were exposed to a series of enzymes. The endoproteinase Glu-C mimicked the inhibition produced by the light chain. Second, protease inhibitors of different specificities were assessed for blockade of the action of light chain on [3H]-noradrenaline release from permeabilized cells. Blockade was complete with EDTA (2.5 mmol/l) or 1,10-o-phenanthroline (1 mmol/l), and absent with the highest concentrations tested of diisopropylfluorophosphate, phenylmethylsulfonyl fluoride, pepstatin, leupeptin, bestatin, phosphoramidon, thiorphan or trans-epoxysuccinic acid (E64) which is regarded as an inhibitor of thiol proteases. This inhibitor spectrum suggested that light chain might be a metalloprotease. Finally a sequence-His-Glu-Leu-X-His-occurring in the light chains of tetanus toxin and of the botulinum neurotoxins A, C, D, E was also found in many endoproteinases and an aminopeptidase. The motif is known to constitute their active site and to bind Zn2+. In fact Zn2+ (0.6-0.9 mol/mol) was found in thoroughly dialysed two-chain tetanus toxin. The three approaches jointly support the hypothesis that the light chain of tetanus toxin, and probably of all clostridial neurotoxins, inhibits [3H]-noradrenaline release from adrenomedullary cells by degradation of (a) specific, still unknown protein(s) involved in exocytosis.

Adrenal Medulla↗