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PubMed2005

Antibody titers and immune response to diphtheria-tetanus-pertussis and measles-mumps-rubella vaccination in children treated for acute lymphoblastic leukemia.

The objective of this study was to investigate the diphtheria-tetanus-pertussis and/or measles-mumps antibody titers before and after vaccination at various time points of acute lymphoblastic leukemia (ALL) therapy and to suggest an appropriate vaccination approach for ALL patients. The authors studied 37 ALL patients and 14 healthy control subjects, divided into three groups. In group 1 (newly diagnosed patients), baseline anti-diphtheria, anti-tetanus, and anti-pertussis titers were determined. Patients in group 2 (on maintenance chemotherapy) and group 3 (patients not receiving therapy for 3-6 months) were vaccinated with diphtheria-tetanus with or without acellular pertussis; group 3 and control subjects were also given measles-mumps-rubella vaccine. Preimmunization and 1-month postimmunization titers were drawn. Preimmunization anti-diphtheria and anti-tetanus antibody titers between the groups and the controls were statistically similar. The seropositivity rate for anti-measles antibody in group 3 was significantly lower than controls. After vaccination, all of the patients developed protective anti-diphtheria and anti-tetanus antibody titers. The seroconversion rates of group 3 and controls for anti-measles and anti-mumps antibodies were statistically similar. The results showed that patients on maintenance therapy and after cessation of therapy made good antibody responses to diphtheria and tetanus toxoids, but response to measles and mumps vaccines was not as sufficient as toxoid vaccines. Children with ALL can receive the appropriate vaccines during and after maintenance treatment.

Adolescent↗
PubMed1984

Low pH induces a hydrophobic domain in the tetanus toxin molecule.

Binding of the non-ionic detergent [3H]Triton X-100 by tetanus toxin, by its fragment C and by its alpha chain has been studied. At pH 4.00 or above, tetanus toxin does not bind Triton X-100. At pH lower than 4.00, binding of detergent to the toxin occurs. At pH 3.00, a maximum of 100 mol bound/mol of protein is reached only when the detergent concentration exceeds its critical micelle concentration. No measurable amount of Triton X-100 is bound by the toxin C fragment at pH 3.00. Most of the tetanus toxin alpha chain precipitates out in Triton X-100 at pH 3.00. Leakage of K+ from single-walled asolectin vesicles loaded with potassium was observed with tetanus toxin at pH lower than 4.00. When ganglioside GDlb was present on the asolectin vesicles, release of K+ was obtained with tetanus toxin between pH 4.00 to 5.00. We suggest that, as for diphtheria toxin, entry of tetanus toxin into an acidic compartment of target cells might be required for the expression of its biological activity.

Gangliosides↗
PubMed1989

Isolated light chain of tetanus toxin inhibits exocytosis: studies in digitonin-permeabilized cells.

Previous work indicates that the heavy chain of tetanus toxin is responsible for the binding of the toxin to the neuronal membrane and its subsequent internalization. In the present study, the light chain of tetanus toxin mimicked the holotoxin in inhibiting Ca2+-dependent secretion of [3H]norepinephrine from digitonin-permeabilized adrenal chromaffin cells. Preincubation of tetanus toxin with monoclonal antibodies to the light chain prevented the inhibition by tetanus toxin. Preincubation of tetanus toxin with nonimmune ascites fluid or with monoclonal antibodies directed against the C fragment (the C-terminal of the heavy chain) or the heavy-chain portion of the B fragment did not prevent inhibition by tetanus toxin. The data indicate that the light chain is responsible for the intracellular blockade of exocytosis.

Adrenal Medulla↗
PubMed1989

Electroencephalography in tetanus.

To assess the brain involvement caused by tetanus, we examined the EEGs of 39 patients recovered from tetanus and those of 39 sex- and age-matched controls. The patients had significantly more frequent and more severe EEG abnormalities than their controls. The most marked difference was in the occurrence of diffuse EEG abnormalities (P less than 0.05). Twenty patients had normal EEGs. EEGs of 14 patients (5 of whom in this follow-up) during acute tetanus showed abnormalities in 10 patients, marked in degree in 3 of those. EEG abnormalities started to improve after the acute phase of tetanus. It is concluded that EEGs of patients with tetanus are often abnormal and that EEG is helpful in revealing brain involvement in patients after tetanus.

Adult↗
PubMed1991

Long-term follow-up of children born to women immunized with tetanus toxoid during pregnancy.

Ten years after transplacental immunization with tetanus toxoid, the antibody responses of the immunized children to a booster immunization with 5 Lf tetanus toxoid did not differ from those of the control children. The tetanus toxoid-stimulated lymphocyte proliferative responses showed that there was no tolerance to tetanus toxoid induced by transplacental immunization, and the stimulation indices suggested that there may be some long-term memory for tetanus toxoid among the T lymphocytes in children who had been transplacentally immunized by maternal immunization with a standard dose of tetanus toxoid.

Antibodies, Bacterial↗
PubMed1992

Restoration of exocytosis occurs after inactivation of intracellular tetanus toxin.

Tetanus toxin blocks carbachol-stimulated release of noradrenaline from bovine adrenal chromaffin cells in culture, provided it can gain access to the cells. This can be achieved by electropermeabilization of the plasma membrane or by enriching the membrane with exogenous gangliosides which serve as carriers of the toxin. The inhibition of noradrenaline release persists for at least 6 days, even in the presence of specific anti-tetanus toxin antibodies in the culture medium. However, the block is preventable, for the most part, when antibodies enter chromaffin cells during electropermeabilization, before the uptake of the toxin is facilitated by inserting exogenous gangliosides into the plasma membrane 2 days later. This indicates that the antibodies pass into the cells through the physically induced pores and that these intracellular antibodies neutralize incoming tetanus toxin. If, on the other hand, exocytosis has been inhibited by tetanus toxin, it will recover within 3 days, provided specific anti-tetanus toxin antibodies are introduced into the cells by electropermeabilization. The recovery is not linked to a specific route of entry of the toxin. It is concluded that the restoration of noradrenaline release requires not only the intracellular neutralization of tetanus toxin but also the reconstitution of the as yet unknown target molecule of the toxin.

Adrenal Glands↗
PubMed1979

Intensive care in tetanus: management, complications, and mortality in 100 cases.

One hundred cases of tetanus were treated in the intensive care unit of Leeds General Infirmary during during 1961--1977. In 90 patients disease was severe enough to require paralysis and artificial ventilation; a further three needed tracheostomy but not paralysis; and in seven the condition was mild, requiring sedation only. Ten patients died, but all deaths were attributable to complications of treatment rather than to the disease itself and were theoretically avoidable. No evidence of permanent neurological damage from tetanus was found. In 65 patients a wound was the source of infection, most of which were minor, often receiving no medical attention. In five patients the source was probably varicose ulcers of the leg. Such patients, if lacking immunity, are at risk, particularly when farming or gardening. Only two patients had received a full course of tetanus toxoid, in one case eight years and in the other three years before injury; neither received a booster dose at the time of injury and in the second tetanus was mild. Of the 35 patients who did seek medical attention at the time of wounding, 21 received prophylactic antibiotics and 25 tetanus toxoid, but none received equine or human antitetanus serum. Early resort to tracheostomy and paralysis in severe tetanus resulted in a favourable mortality of 10% in the series. To implement such a policy full intensive-care facilities, with a trained nurse to care for each patient, must be available at all times.

Adolescent↗
PubMed1998

Tetanus in the elderly: is it different from that in younger age groups?

Our aims were to itemize the clinical features and the outcome of tetanus in the elderly, as well as any age and sex differences in its acquisition. Therefore, we compared the demographic and clinical data of 12 elderly (group 1) cases of tetanus with 69 middle-aged patients (group 2) and 12 children (group 3) suffering from the same disease. There was no significant difference between the site of entry and incubation period or in the clinical and paraclinical findings among the three groups of patients. Acute respiratory failure was found more commonly in group 1 than in groups 2 and 3 (p = 0.0167 and p = 0.0006, respectively). It was also more common in group 2 than in group 3 (p = 0.0140). A mild form of tetanus was more often detected in children than in middle-aged and elderly cases (p = 0.0213 and p = 0.0013, respectively). Severe tetanus was seen more often in group 1 than in groups 2 and 3 (p = 0.0167 and p = 0.0006, respectively). Despite this, the mortality rate was not statistically different among the three groups of patients. Females were affected much less frequently than males with a female:male ratio of 1:3 in all three age groups. Our results suggest that elderly patients are at higher risk of acquiring a more severe form of tetanus and the subsequent development of acute respiratory failure. In addition, the disease is more common in males of all age groups, and age and sex have no apparent effect on the outcome of patients with tetanus.

Acute Disease↗
PubMed1986

Efficacy of dantrolene sodium in management of tetanus in children.

The effectiveness of dantrolene sodium in controlling tetanic spasms was evaluated in 21 children (aged 4 days-13 years) with tetanus. These dantrolene-treated patients were compared with an historical control group of 26 children previously treated for tetanus by traditional means at the same institution. The groups were comparable in terms of age, other treatments, and severity of disease. All patients received standard treatments for tetanus, including sedatives, antibiotics, and tetanus-immune globulin. Patients in the dantrolene-treated group also received dantrolene, either intravenously (Dantrium Intravenous) or orally, in divided doses totalling 4-6 mg/kg/day. Mortality was 73% (neonates 83%, non-neonates 50%) in the control group, compared with 33% (neonates 50%, non-neonates 0%) in the dantrolene-treated group. Dantrolene did not cause additional respiratory depression when administered alone or in combination with other drugs routinely used to treat tetanus. In this study, the use of dantrolene with traditional conservative therapy significantly reduced mortality from tetanus.

Adolescent↗
PubMed2001

Black tea extract, thearubigin fraction, counteracts the effect of tetanus toxin in mice.

The aim of this study was to find an inactivating substance for tetanus toxin in natural foodstuff. Tetanus toxin (4 micrograms/ml) abolished indirect twitches in In vitro mouse phrenic nerve-diaphragm preparations within 2.5 hr. Hot water infusion of black tea mixed with tetanus toxin blocked the inhibitory effect of the toxin. Mixing the toxin with thearubigin fraction extracted from black tea infusion produced an identical result. Furthermore, thearubigin fraction mixed with the toxin protected against the in vivo paralytic effect of the toxin. Thearubigin fraction had no protective effect on other toxins, such as tetrodotoxin and saxitoxin. The specific binding of [125I]tetanus toxin to rat cerebrocortical synaptosomes was inhibited by mixing iodinated toxin with thearubigin fraction. These results imply that thearubigin fraction counteracts the effect of tetanus toxin by binding with toxin, and also suggest that this fraction may be able to apply for prophylaxis of tetanus.

Animals↗
PubMed2005

Tetanus toxoid-loaded transfersomes for topical immunization.

Topical immunization is a novel immunization strategy by which antigens and adjuvants are applied topically to intact skin to induce potent antibody and cell-mediated responses. Among various approaches for topical immunization, the vesicular approach is gaining wide attention. Proteineous antigen alone or in combination with conventional bioactive carriers could not penetrate through the intact skin. Hence, specially designed, deformable lipid vesicles called transfersomes were used in this study for the non-invasive delivery of tetanus toxoid (TT). Transfersomes were prepared and characterized for shape, size, entrapment efficiency and deformability index. Fluorescence microscopy was used to investigate the mechanism of vesicle penetration through the skin. The immune stimulating activity of these vesicles was studied by measuring the serum anti-tetanus toxoid IgG titre following topical immunization. The immune response was compared with the same dose of alum adsorbed tetanus toxoid (AATT) given intramuscularly, topically administered plain tetanus toxoid solution, and a physical mixture of tetanus toxoid and transfersomes again given topically. The results indicated that the optimal transfersomal formulation had a soya phosphatidylcholine and sodium deoxycholate ratio of 85:15%, w/w. This formulation showed maximum entrapment efficiency (87.34 +/- 3.81%) and deformability index (121.5 +/- 4.21). An in-vivo study revealed that topically administered tetanus toxoid-loaded transfersomes, after secondary immunization, elicited an immune response (anti-TT-IgG) comparable with that produced by intramuscular AATT. Fluorescence microscopy revealed the penetration of transfersomes through the skin to deliver the antigen to the immunocompetent Langerhans cells.

Administration, Cutaneous↗
PubMed2005

Synaptic targeting of retrogradely transported trophic factors in motoneurons: comparison of glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, and cardiotrophin-1 with tetanus toxin.

Glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and cardiotrophin-1 (CT-1) are the most potent neurotrophic factors for motoneurons, but their fate after retrograde axonal transport is not known. Internalized trophic factors may be degraded, or they may be recycled and transferred to other neurons, similar to the known route of tetanus toxin. We tested whether neonatal rat hypoglossal motoneurons target retrogradely transported trophic factors to synaptic sites on their dendrites within the brainstem and subsequently transfer these trophins across the synaptic cleft to afferent synapses (transsynaptic transcytosis). Motoneurons retrogradely transport from the tongue radiolabeled GDNF, BDNF, and CT-1 as well as tetanus toxin. Quantitative autoradiographic electron microscopy showed that GDNF and BDNF were transported into motoneuron dendrites with labeling densities similar to those of tetanus toxin. Although tetanus toxin accumulated rapidly (within 8 h) at presynaptic sites, GDNF accumulated at synapses more slowly (within 15 h), and CT-1 never associated with synapses. Thus, some retrogradely transported neurotrophic factors are trafficked similarly but not identically to tetanus toxin. Both GDNF and BDNF accumulate at the external (limiting) membrane of multivesicular bodies within proximal dendrites. We conclude that tetanus toxin, GDNF, and BDNF are released from postsynaptic sites and are internalized by afferent presynaptic terminals, thus demonstrating transsynaptic transcytosis. CT-1, however, follows a strict degradation pathway after retrograde transport to the soma. Synaptic and transcytotic trafficking thus are restricted to particular neurotrophic factors such as GDNF and BDNF.

Animals↗
PubMedDate not supplied

Effect of tetanus immunization on t-helper cytokine production in adults with and without allergic rhinitis.

Epidemiological evidence links T-helper type 2 (Th2) cytokine responses to the pathogenesis of atopy/asthma. It is hypothesized that certain immunizations may induce/amplify Th2 cytokine responses. The objective of this study was to determine whether Th cytokine responses to immunization with tetanus toxoid differ in adults with and without allergic rhinitis (AR). Thirty subjects were enrolled (15 AR and 15 non-AR subjects as confirmed by history and allergy skin testing). Blood was collected before (day 0) and on days 3, 7, 14, and 28 after immunization with tetanus toxoid. Peripheral blood mononuclear cells (PMNCs) were purified and cultured with either PHA or tetanus toxoid for 2 or 6 days, respectively. Supernatants were harvested and assayed for IFN-gamma and IL-13 levels (pg/mL) by EIA. Results were normalized by log transformation and analyzed by stepwise regression. Baseline (day 0) cytokine values were similar in both groups. PHA and tetanus-induced IFN-gamma were increased (p < 0.05) in non-AR (3.2 +/- 0.3 and 1.4 +/- 0.3 on day 7, and 3.5 +/- 0.2 and 1.9 +/- 0.2 on day 14, respectively) compared with AR subjects (2.3 +/- 0.3 and 0.9 +/- 0.3 on day 7, and 2.7 +/- 0.3 and 1.2 +/- 0.3 on day 14, respectively). PHA-induced, but not tetanus-induced, IL-13 production was increased (p < 0.05) in non-AR compared with AR subjects on day 7 (p < 0.05). PHA-induced IL-13 production was 3.1 +/- 0.2 in non-AR and 2.6 +/- 0.3 in AR subjects on day 7. These results indicate differential Th cytokine responses in AR and non-AR subjects after immunization with tetanus toxoid. Future studies are warranted and may result in the identification of potential prevention/treatment strategies for atopy/asthma.

Adolescent↗
PubMed2002

A case of maternal tetanus in Korea.

Tetanus is uncommon in Korea due to the introduction of vaccination programs and advances in public health. A case of maternal tetanus occurred on the 9 day postpartum in a 29-yr-old woman, who had not received a 10-yr-booster of tetanus-diphtheria toxoid after receiving the primary series of tetanus-toxoid-containing vaccine. There has hitherto been no reports on maternal tetanus in Korea. This case illustrates that tetanus remains a medical problem, principally among non- and under-immunized adults. The only way to fully prevent this disease is to ensure adequate immunization in all adults.

Adult↗
PubMed1995

Short report: the spatula test: a simple bedside test to diagnose tetanus.

Four hundred patients with suspected tetanus were studied to determine the value of the spatula test to diagnose tetanus. A positive test result (reflex spasm of the masseters on touching the posterior pharyngeal wall) was seen in 359 (94%) of 380 patients with tetanus and in no patient without tetanus. Thirty-three of 400 patients (13 with tetanus and 20 with other diagnoses) had a negative test result (a gag reflex with attempted expulsion of the spatula). Thus, the test performed on presentation had a high specificity (100%) and sensitivity (94%) for diagnosing tetanus.

Adult↗
PubMed1999

Transport of cationized anti-tetanus Fab'2 fragments across an in vitro blood-brain barrier model: involvement of the transcytosis pathway.

Tetanus neurotoxin reaches the CNS by axonal retrograde transport and thus becomes inaccessible to current treatments. A possible strategy to improve current therapy for tetanus disease would be the vectorization of Fab'2 fragments, allowing their delivery into the CNS. The purpose of this study was to investigate whether after cationization anti-tetanus Fab'2 fragments are able to cross the blood-brain barrier, the first obstacle to CNS delivery. We used primary cocultures of bovine brain capillary endothelial cells and newborn rat astrocytes as an in vitro model to study the binding and transport of cationized Fab'2 (cFab'2) fragments across the brain endothelium. We first show that cationization does not alter Fab'2 affinity for tetanus toxin. Then we demonstrate that after cationization Fab'2 fragments are able to bind to the negative charges on the surface of endothelial cells and subsequently to be transported across the endothelial cell monolayer without any modification of affinity. Finally, using fluorescence microscopy, we show that cFab'2 fragments are transported through endocytotic vesicles. The present study demonstrates that cationization allows Fab'2 directed against tetanus toxin to be transported through brain endothelium by adsorptive-mediated transcytosis. We suggest that this vectorization way could be a promising delivery strategy for carrying anti-tetanic immunoglobulin fragments across the blood-brain barrier to improve tetanus treatment.

Animals↗
PubMedDate not supplied

Development and validation study for the chromatographic purification process for tetanus anatoxin on Sephacryl S-200 High Resolution.

The tetanus purified anatoxin is used in the preparation of multiple immunoprophylactics. WHO (World Health Organization) specifies that the tetanus anatoxin must exhibit a degree of purity greater than or equal to 1,000 Lf/mg protein nitrogen (PN). Today liquid chromatography is a well established technique for the purification of tetanus anatoxin and several different methods are used in production scale. On a small scale, we purified tetanus anatoxin on Sephacryl S-200 High Resolution (gel filtration) and we obtained a successful high-yield purification. On the basis of these results, by combining conventional tangential flow filtration (TFF) at 50,000 N.M.W.L. (Nominal Molecular Weight Limit) ultrafiltration membrane with gel filtration on Sephacryl S-200 High Resolution, we have been able to purify 14 lots of tetanus anatoxin using the Bioprocess System (Amersham Pharmacia Biotech) to a large scale operation. Using this method, 77,401,332 doses of tetanus toxoid were prepared in 14 consecutive lots, supporting the reproducibility and reliability of the method presented here.

Acrylic Resins↗
PubMed1999

Tetanus: study of 8,697 cases.

Records of 8,697 cases of tetanus seen over a period of 14 years are analysed. Overall mortality was 48.0%. Mortality in neonatal group was 86.38% whereas that in non-neonatal group it was 40.18%. Disease was seen more frequently in male than in female. Mortality in male was lower than in female. Incidence was highest in the first decade of life. Mortality was lowest (about 33%) in first two decades (excluding neonatal group). Mortality in neonatal group was highest (86.38%). Mortality was inversely related to length of incubation period. In cases with incubation period of 7 days or less, mortality was 58.26% in non-neonates and 94.15% in neonates. Mortality was very low (2.14%) in 2,100 cases who did not develop spasms. In cases with spasms mortality was inversely related to the length of period of onset. Temperature of 100 degrees F within first 24 hours of admission was an adverse factor and these cases had higher mortality. Cases were divided into five grades according to the severity. Mortality in each grade was significantly different from that in the other. Mortality was lower in otogenic tetanus while it was higher in post-abortion and post-injection tetanus. Tetanus following penetrating injury carried higher mortality whereas tetanus following abrasions had lower mortality. With head and face as the site of infection, mortality was low while it was high when the site of infection was a trunk. Results were similar with dose of A.T.S. ranging between 5,000 and 60,000 i.u. and tetanus immune globulin, whereas mortality was high with higher and lower dose of A.T.S. or with no A.T.S. Respiratory spasms, respiratory failure, respiratory complications and circulatory failure were the common causes of death.

Adolescent↗