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PubMed1985

Attenuation of inhibitory processes in the central nervous system by tetanus toxin: an in vitro study on rat hippocampal slices.

The influence of tetanus toxin on the efficiency of recurrent inhibition in the rat hippocampal slice was tested. The efficiency of the recurrent inhibition diminished in a dose-dependent manner following incubation of the slices with tetanus toxin. The effect was not observed in the slices preincubated for 3 hours with neuraminidase from Vibrio cholerae. This treatment reduces markedly the level of polysialogangliosides (receptor for tetanus toxin). It is concluded that tetanus toxin influences the efficiency of some inhibitory synapses in the central nervous system and that a certain level of polysialogangliosides is necessary for tetanus toxin to exert its action.

Action Potentials↗
PubMed1991

High vulnerability of dentate granule cells to the neuropathological effects induced by intrahippocampal injection of tetanus toxin.

The behavioural and neuropathological effects of tetanus toxin, injected into the dentate gyrus, were studied in rats. The monolateral injection of a single dose (1000 mouse minimum lethal doses, MLDs; n = 14 rats) of tetanus toxin produced time-dependent behavioural stimulation. Wet-dog shakes and facial stereotypy were observed 3-4 days after the injection, culminating 4-5 days after treatment, in "limbic motor seizures". Ten days after injection, histological examination revealed death of dentate granule cells in the tetanus toxin-treated side but not in the contralateral, control side (treated with neutralized toxin). This effect was observed in all rats (n = 5) receiving tetanus toxin in the dentate gyrus and no damage was reported in other sectors (e.g. CA1 and CA3 pyramidal cell layers) of the hippocampus. Quantification of the neuronal damage yielded an approximately 70% reduction (P less than 0.01) in the number of granule cells in the toxin-injected dentate gyrus, compared with the control side. This was greater than that previously reported (30% reduction) in the CA1 pyramidal cell layer of rats receiving the same dose of toxin, into the regio superior of the hippocampus. In conclusion, the present experiments have shown that the focal injection of tetanus toxin into the dentate gyrus produced behavioural excitation and selective death of dentate granule cells.

Animals↗
PubMed1993

Disulfide formation in reduced tetanus toxin by thioredoxin: the pharmacological role of interchain covalent and noncovalent bonds.

The interchain disulfide bond of tetanus toxin is known to be cleaved by reduced thioredoxin and by rat brain homogenate. We now show that this bond, but not the disulfide loop in the heavy chain of the toxin, can be restored quickly and completely by oxidized thioredoxin. Oxidized glutathione was at least 100 times less potent and less specific. Reduced tetanus toxin did not measurably (KD below 50 nM) dissociate into its chains, as revealed by HPLC gel chromatography under nondenaturing conditions. Accordingly, when the reduced toxin or its recombined chains were injected into mice, general toxicity was diminished but not abolished, as compared with the native form. Inhibition of Ca(2+)-evoked [3H]noradrenaline release was assayed in cultured adrenomedullary cells after permeabilization with digitonin. Reduced two-chain tetanus toxin was as active as the isolated light chain in this system, and the action of the light chain was only slightly diminished by the addition of excess heavy chain. The results show that thioredoxin can both open and close the covalent bond between the chains of tetanus toxin, and that the reduced chains remain linked by noncovalent forces. The role of the thioredoxin system for reversible activation of tetanus toxin in vivo remains to be established.

Adrenal Medulla↗
PubMed1995

Tetanus immunization and its association to hepatitis B vaccination in patients with chronic renal failure.

A defect in the immune response of patients with chronic renal failure leads to low response rates and insufficient antibody concentrations following a number of highly recommended vaccinations. This has been shown before for immunization against hepatitis B and influenza. Few data are available concerning the efficacy of vaccination with tetanus toxoid in these patients. In a prospective, controlled study we vaccinated seronegative patients with chronic renal failure not on dialysis, patients on chronic intermittent hemodialysis, and patients after kidney transplantation with tetanus toxoid. The results were compared with those of a control group consisting of 13 age-matched patients with mild essential hypertension and normal kidney function. Only 11 of 20 (55%) patients in the chronic renal failure group and 16 of 23 (69%) in the dialysis group had a protective antibody response after triple vaccination. In contrast, all the patients in the control group and six of seven transplant patients seroconverted. The response to tetanus toxoid was highly associated with the response to a previously administered vaccination against hepatitis B. Responders to this vaccination also had a better response rate to tetanus toxoid. The antibody concentrations after vaccination were lower in all patient groups compared with the controls; the lowest titers were found in the transplant patients. Therefore, renal patients will need revaccination much earlier, and tetanus toxoid antibody levels should be checked if a patient is injured and potentially requires vaccination.

Adult↗
PubMed1984

The dynamics of tetanus epidemiology and control in rural Uttar Pradesh studied through computer simulation.

An epidemiological model is constructed for tetanus. The assumptions as well as the steps involved in the construction of the model, are detailed. The impact of alternate immunisation strategies to control tetanus in rural Uttar Pradesh, is studied using this model. The quantification of the expected decline in incidence and mortality over 30 years, for different control strategies, provides the health planner with valuable information. It is seen that the incidence of tetanus neonatorum and tetanus in adults, as well as deaths due to tetanus, progressively decreases as the level of coverage is increased. The most marked reduction is seen over the initial period of intervention. Mass immunisation of the total population, or of just the females in the reproductive age group, leads to temporary decline in the endemic level. Such models are useful for planning in the health sector in India since, they can be constructed with the limited information available.

Adult↗
PubMed1988

Cephalic tetanus: a case report and review of the literature.

Cephalic tetanus is a rare form of tetanus defined as trismus plus paralysis of one or more cranial nerves. The most frequently involved cranial nerve is the seventh. It accounts for 1 to 3% of the total number of reported cases of tetanus and has a mortality of 15 to 30%. The incubation period is 1 to 14 days, and approximately two thirds of cases progress to generalized tetanus. The mechanism of the paralysis is not completely understood. Treatment involves debridement of wounds, administration of penicillin and tetanus immune-globulin, aggressive supportive care, and initiation of active immunization.

Facial Injuries↗
PubMed1992

Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin.

We examined glutamate-mediated neurotoxicity in cortical cell cultures pretreated with 1-5 micrograms/ml tetanus toxin to attenuate the Ca(2+)-dependent release of neurotransmitters. Efficacy of the tetanus toxin pretreatment was suggested by blockade of electrical burst activity induced by Mg2+ removal and by reduction of glutamate efflux induced by high K+. Tetanus toxin reduced neuronal injury produced by brief exposure to elevated extracellular K+ or to glutamate, situations in which release of endogenous excitatory neurotransmitter is likely to play a role. Furthermore, although glutamate efflux evoked by anoxic conditions may occur largely via Ca(2+)-independent transport, tetanus toxin attenuated both glutamate efflux and neuronal injury following combined oxygen and glucose deprivation. With prolonged exposure periods, the neuroprotective efficacy of tetanus toxin was comparable to that of NMDA receptor antagonists. Presynaptic inhibition of Ca(2+)-dependent glutamate release may be a valuable approach to attenuating hypoxic-ischemic brain injury.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Sustained and selective block of IPSPs in brain slices from rats made epileptic by intrahippocampal tetanus toxin.

A small dose of tetanus toxin (2-5 ng; 10 mouse LD50) injected into the rat hippocampus produces a chronic epileptic syndrome in which epileptic discharges recur intermittently for 6-8 weeks. Hippocampal slices prepared during this period and maintained in vitro generate both evoked and spontaneous epileptic discharges. The present study used slices prepared 8-18 days after injection of tetanus toxin or vehicle solution into both hippocampi to test whether or not synaptic inhibition was selectively impaired in this experimental epilepsy. Intracellular recordings were made from CA3 pyramidal layer neurones within the tetanus toxin focus, which was identified by field potential recordings of synchronous bursts evoked by afferent stimulation. The intrinsic properties of these neurones did not differ from comparable cells in control-injected rats. All cells generated excitatory postsynaptic potentials (EPSPs) following stimulation of stratum radiatum in CA3. In control slices EPSPs were followed by a 'fast' inhibitory postsynaptic potential (IPSP), peaking at 25-30 ms, with a mean amplitude (+/- SEM) of -6.7 mV (+/- 0.66). In the epileptic slices these were absent, and the EPSP prolonged so that the potential at 30 ms was a depolarisation of +6.6 mV (+/- 2.75). The slow IPSP at 120 ms dropped to -0.27 mV (+/- 0.18) from -3.97 mV (+/- 1.43) (11 cells in each group). The loss of IPSPs cannot be attributed to a shift in reversal potentials in the toxin-injected group because no IPSPs were unmasked by current injection (n = 11). IPSPs also occurred spontaneously in the neurones in control slices, with a mean amplitude of -1.30 mV. Their frequency decreased by a factor of 13 in cells from the chronic focus induced by tetanus toxin (P less than 0.0001, analysis of variance), but their amplitude did not change significantly (mean of -1.22 mV). Spontaneous EPSPs were significantly more frequent and slightly smaller in the toxin-injected group (mean amplitudes 1.35 and 1.13 mV respectively). Together these studies support the hypothesis that the chronically recurring seizures induced by low doses of tetanus toxin can be attributed to a substantial, persistent and selective reduction of inhibitory neurotransmission in the hippocampus.

Animals↗
PubMed2004

Is there a causative role for tetanus toxoid vaccination in the development of allergy-like symptoms and in the increasing prevalence of atopic diseases?

Allergic diseases are a worldwide health problem. They mainly affect people living in developed countries where an increasing prevalence of allergy symptoms has been recorded in the last 20-30 years. The cause of this increase is still disputed, and, among others, the "hygiene hypothesis" supported the concept that relevant changes in lifestyle could have a relationship with the phenomenon. More recently the recorded parallel increase in autoimmune diseases has suggested to consider the "hygiene hypothesis" as a cause of a more general disregulation of the immune system leading to both allergy and to autoimmunity. Here are reported a series of observations, evidence, and data from the literature leading to a different hypothesis. The key points are: (1) the presence of two subsets of patients having allergy symptoms based on an IgE-mediated mechanism or not; (2) the positive results obtained with the autologous serum skin test in either cutaneous or respiratory affected subjects, mainly in children and adult females; (3) the presence of IgG autoantibodies against the alpha-chain of the high affinity IgE receptor (FcepsilonRIalpha) in non-IgE-mediated urticaria and even in respiratory subjects; (4) the cross-reactivity between epitopes of the tetanus toxoid molecule and the FcepsilonRIalpha detected by means of an alpha-chain affinity purified IgG fraction; (5) the positive skin reactivity obtained using IgG anti-tetanus toxoid preparations in allergic and non-allergic volunteers. The presence of IgG autoantibodies actively generated by the population-based vaccination with tetanus toxoid could induce both mediator release from activated mast cell and Th2 cytokine production early in life. There are epidemiological evidences that tetanus toxoid vaccination could be linked with an increased tendency to have allergy symptoms. The different epidemiological distribution of non-IgE-mediated symptoms, mainly affecting young infants would be in agreement with the present hypothesis. The prevalent mother-to-child relationship in terms of risk for allergy symptoms could be explained with the trans-placenta transfer of IgG. A similar transfer could also take place through the mother milk during breast feeding. It may thus be hypothesized that the increased prevalence of allergic diseases could be caused by the generalized tetanus toxoid immunization procedure, progressively extended to most of the countries worldwide in the last 30-40 years. Both the induction of non-IgE-mediated symptoms caused by the mast cell activation via the anti-FcepsilonRIalpha IgG and the long lasting Th2 inflammation of affected tissues would be the inducing mechanisms. This hypothesis would re-configure part of the allergic diseases as a Th2 phenotypic expression of an autoimmune disease.

Causality↗
PubMed2004

Impact of improved vaccination programme and intensive care facilities on incidence and outcome of tetanus in southern Vietnam, 1993-2002.

Unvaccinated individuals throughout the world are vulnerable to tetanus, but there are few data regarding the impact of focused vaccination programmes and modern intensive care facilities on the disease, particularly in the developing world. The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam admitted 2422 patients with tetanus aged > or =1 year between April 1993 and December 2002, during which time vaccine coverage and treatment facilities improved. The proportion of children < or =10 years old admitted with tetanus fell from 11.1 to 5.6% over the 10 year period (P = 0.002). The proportion of women aged 20-40 years fell from 10.1 to 1.2% (P < 0.001). Mortality rates fell from a maximum of 27.81% in 1994 to 10.04% in 2002 (P < 0.001). Thus, a marked reduction in tetanus incidence has occurred in age groups specifically targeted by the national vaccination programme. However, tetanus continues to be a major cause of morbidity and mortality in individuals outside the target population. Improved intensive care facilities, such as mechanical ventilation and low-cost infection control procedures are associated with a significant reduction in mortality.

Adolescent↗
PubMed1999

Effects of tetanus toxin on functional inhibition after injection in separate cortical areas in rat.

Tetanus Toxin is widely used as a model of chronic focal epilepsy and is assumed to act by blocking neurotransmitter release with high selectivity for inhibitory synapses. However, the exact mechanisms are not fully understood, since, e.g., GABA release is only temporarily decreased although epileptiform activity persists pointing towards a change in the interplay of excitation and inhibition. Furthermore there have been reports about different effects of tetanus toxin after injection in separate brain areas. Therefore, we investigated the functional inhibition after injecting tetanus toxin either in the motor or sensory cortex of adult rats by using a paired-pulse paradigm as a measure of excitatory and inhibitory drive. Tetanus toxin injection into the motor cortex (n=10) induced a marked, long-lasting reduction in inhibition which was highly significant in most parts of the injected cortical area. Injections into the sensory cortex, however, showed less marked changes in inhibition which were more widespread and significant only in 3 of 14 animals injected. These results give further evidence for a prominent effect of tetanus toxin on functional inhibition and strengthen the idea of a differential effect in separate cortical areas. They may be accounted for by the different cytoarchitecture of cortical areas with variable inhibitory and excitatory intracortical connections.

Analysis of Variance↗
PubMed1997

Puerperal tetanus and hysterectomy.

OBJECTIVES: To compare the clinical course and outcome of patients with post-partum tetanus (n = 21) to those of non-post-partum ones (n = 24) and to determine the effect of early hysterectomy on the survival of cases with severe post-partum tetanus (n = 20). METHODS: In this prospective study we compared the clinical course and outcome of post-partum and non-post-partum cases of tetanus admitted to the intensive care unit. Moreover, early hysterectomy was done on every other patient with severe post-partum tetanus (n = 10). Chi-square and Student's t-tests were used for statistical purposes. RESULTS: Post-partum cases were younger (P = 0.002), had a higher incidence of acute respiratory failure and a mortality rate compared to the non-post-partum group. In addition, early hysterectomy did not change the course of severe post-partum cases. CONCLUSION: The mortality associated with post-partum tetanus is comparable to non-post-partum cases and early hysterectomy has no effect on its outcome.

Adult↗
PubMed1988

Clinical and immunologic responses to the capsular polysaccharide of Haemophilus influenzae type b alone or conjugated to tetanus toxoid in 18- to 23-month-old children.

The safety and immunogenicity of Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) alone, or covalently bound to tetanus toxoid in saline solution (Hib-TT) or adsorbed onto AI(OH)3 (Hib-TT ads), were evaluated after one injection into 18- to 23-month-old healthy children in Sweden. No side reactions were elicited by Hib CPS; side reactions elicited by the two conjugates were similar and comparable to those reported for diphtheria and tetanus toxoids adsorbed. Hib-TT was the most immunogenic of the three vaccines, eliciting about 10-fold higher antibody levels than Hib CPS; of 28 vaccinees, all had greater than 1.0 microgram Ab/mL serum after immunization with Hib-TT. Increases of Hib CPS antibodies within immunoglobulin classes induced by the three vaccines were, in decreasing order, IgG greater than IgM greater than IgA. Within IgG subclasses, rises in IgG1 Hib CPS antibodies were the most frequent, followed by IgG2; some vaccinees with high postimmunization levels also had rises in IgG3 and one in IgG4. Immunization-induced Hib CPS antibodies were bactericidal. Hib-TT also elicited higher levels of tetanus toxoid antibodies than Hib-TT ads; these tetanus toxoid antibodies neutralized tetanus toxin in vivo.

Aluminum Hydroxide↗
PubMed1997

Effect of rIL-2 treatment on anti-tetanus toxoid response in the elderly.

To explore the effects of interleukin-2 (IL-2) treatment in a vaccination protocol in the elderly, we administered low-dose rIL-2 to a group of aged subjects before primary tetanus toxoid immunization. A specific antibody response was detectable in the serum of 6/8 treated individuals after primary immunization, but in only 2/6 untreated controls; following antigenic boosting, specific antibody levels remained relatively unchanged in all the seroconverters. The data were confirmed by studying the ability to produce tetanus-specific antibodies in vitro, and by isoelectrofocusing analysis of serum anti-tetanus antibodies; this latter study showed a more restricted clonal response to the immunogen in untreated individuals. On the other hand, the study of the in vitro proliferative response to tetanus toxoid did not evidence clear differences between the two groups. On the whole, these data seem to indicate that a short-term rIL-2 treatment is able to potentiate the antibody response to tetanus toxoid, and may be a useful tool to improve humoral responses to vaccines in aged subjects.

Aged↗
PubMed1994

Role of quinine in the high mortality of intramuscular injection tetanus.

There has been considerable uncertainty about the risks and severity of tetanus after intramuscular quinine, a widely used treatment of severe malaria in the rural tropics. We have compared the clinical features and outcome of tetanus in which injection was the only apparent site of infection with tetanus acquired by other routes in patients admitted to the Centre for Tropical Diseases, Ho Chi Minh City, Vietnam. In 1081 consecutive patients with tetanus treated between Jan 26, 1989, and May 27, 1991, 27 followed intramuscular quinine and 15 followed injections of other drugs. Overall mortality was 26% (285/1081). Mortality in patients who had not had preceding injections was 24% (250/1039) compared with 96% (26/27) in the quinine group (relative risk 4.0, 95% CI 3.5-4.6) (p < 0.0001), and 60% (9/15) in the other injections group (2.5, 1.6-3.8) (p < 0.005). 21 patients (78%) in the quinine group died within 72 h of admission compared with 5 (33%) in the other intramuscular injections group (p < 0.01) and 4 (7%) of 54 matched controls (p < 0.0001). Tetanus that follows intramuscular injections has a poor prognosis, but when it follows intramuscular quinine it is usually rapidly fatal.

Adult↗
PubMed2003

Acceptability of tetanus toxoid vaccine by pregnant women in two health centres in Abidjan (Ivory Coast).

A study was conducted in two health centres in Abidjan, Ivory Coast (Abobo and Port Bouet) to compare the knowledge of pregnant women regarding tetanus and hepatitis B and to evaluate the acceptability of tetanus immunisation. A total of 124 women were interviewed. In spite of Information Education Communication (IEC) meetings held by midwives focusing on both diseases, knowledge about tetanus appeared to be substantially higher than that about hepatitis B. The acceptability of tetanus toxoid vaccine was good, the only barrier being the fear of useless injections. However, the risk of tetanus transmission during delivery should be better explained to women, who often give birth at home in the presence of traditional birth assistants. The awareness of men should also be raised by information campaigns, using different local networks.

Adolescent↗
PubMed1996

Single shot with tetanus toxoid in biodegradable microspheres protects mice despite acid-induced denaturation of the antigen.

Tetanus toxoid encapsulated in microspheres consisting of biodegradable polyesters, prepared by four different manufacturers were evaluated with respect to antigenic load, in vitro release pattern, antigen integrity and immunogenicity. In vitro release studies over periods up to 140 days indicated that only during the first days tetanus toxoid was released. Although some preparations were designed to release their antigen content in a pulsatile manner, this was never observed in vitro. A single immunization with 0.3 Lf tetanus toxoid in microspheres induced substantial humoral responses, in most cases higher than one immunization with plain tetanus toxoid, sometimes higher than one dose of alum-adsorbed toxoid but always lower than booster immunizations. It is shown that the moderate (no booster effect) performance of the microsphere preparations is probably due to acid induced denaturation of the antigen. Despite this drawback, protection level in mice after challenge with 50 LD50 1 year after one immunization with microspheres was, on average, substantially higher than mice receiving plain tetanus toxoid.

Acids↗
PubMed1997

Safety and immunogenicity of an acellular pertussis diphtheria tetanus vaccine given as a single injection with Haemophilus influenzae b conjugate vaccine.

To determine if an acellular pertussis-diphtheria-tetanus vaccine could be combined with a Haemophilus influenzae b conjugate vaccine as a single injection, we randomized 468 children between 17 and 21 months of age previously immunized with three doses of each vaccine to receive a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids, and Haemophilus influenzae b-tetanus toxoid conjugate vaccine either as separate injections on separate days, separate injections on the same day, or as a single combined injection. Rates of adverse reactions were similar amongst the groups except for increased injection site tenderness (29.2% vs 17%, RR 1.76, 95% CI 1.09-2.85) and fussiness (36.4% vs 23.3%, RR 1.59, 95% CI 1.05-2.41) in the group given the combined injection rather than separate injections on separate days. Antibody levels against the capsular polysaccharide of H. influenzae b after the single combined injection (47.1 micrograms ml-1) were lower than after separate injections on the same day (66.0 micrograms ml-1; P < 0.05) but higher than when the injections were administered on separate days (28.4 micrograms ml-1; P < 0.001). We conclude that the five-component acellular pertussis vaccine is safe and immunogenic when combined with diphtheria and tetanus toxoids and H. influenzae b-tetanus toxoid conjugate vaccine in children receiving the fourth dose of the immunization series.

Antibodies, Bacterial↗