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Tetanus in a children's hospital in Addis Ababa: review of 113 cases.

At Ethio-Swedish Children's Hospital Addis Ababa, Ethiopia, children admitted with a diagnosis of tetanus during January 1989- December 1998 were studied. During the 10 year study period there were 113 patients admitted with a diagnosis of tetanus. Sixty two (54.9%) of them were newborns and the rest 51 (45.1%) were children between the age of 1 and 12 years. Fifty six (90.3%) of the newborns were born at home and 43 (69.4%) of the mothers didn't have antenatal care. The median age on admission was 7 days. The umbilicus was assumed to be the portal of entry for all the cases with neonatal tetanus. Forty six (74.2%) of those with neonatal tetanus died in the hospital. Significantly high case fatality rate was seen in neonates with incubation period less than 7 days, onset time 48 hours or less, high pulse rate >140/minute and in those having fever. In non-neonates, the median age at admission was 9 years and the commonest site of entry was lesion on the lower extremities. Sixteen (31.4%) died in the hospital. The outcome was poor in those with onset time of 48 hours or less and in those presenting within 72 hours after the onset of illness. The overall mortality is high. Due attention needs to be given to children with tetanus having poor prognostic factors, particularly among newborns. Antenatal care needs to be promoted. A community based study is recommended to determine the true magnitude of the problem.

Child↗

Tetanus: 20 years of clinical experience.

Tetanus remains a life-threatening disorder and its fulminating course always presents a challenge to the clinician. We retrospectively evaluated 56 patients with tetanus admitted to VGH-Taipei between 1971 and 1990. All of these patients with tetanus on admission showed typical features, with the most common initial complaints being lockjaw and dysphagia (82.6%). They were diagnosed on clinical identification rather than isolation of the causative agent. The laboratory tests were usually nonspecific and of limited value for diagnosis. Overall, 38 patients were seized with tetanus after an identified wound infection. The most common routes were puncture wound (28.3%) and abrasion wound (19.6%). The majority of patients became symptomatic within 10 days (56.5%) and the shorter interval reflected a more overwhelming course (p less than 0.05). Intravenous drug abusers and larger wounds had a poorer prognosis. The average mortality was 39.1% (18 out of 46 patients; male/female 12/6), with lack of statistical difference between sex and mortality (p greater than 0.5). The course of tetanus in the newborn and elderly was also more deadly (mortality rates of 83.3% and 55.6% respectively). Aspiration pneumonia and subsequent respiratory failure accounted for the most common cause (11 cases, 61.1%) of death. The mortality was still high (28.6%) from 1980-90 even with better supportive care and modern therapeutic equipment.

Adolescent↗

[Improvement of the EIA kit for the detection of tetanus immunoglobulin in human sera].

For the program to eliminate tetanus neonatorum in this country, we have improved the sensitivity of enzyme immunoassay kit (EIA kit) prepared on 1987 for the detection of human tetanus immunoglobulin (TIG) by competitive principle. (Chinese J Microbiol Immunol 1987; 20: 269-278) Horse-radish peroxidase-conjugated to tetanus toxoid monoclonal antibody was involved in the new kit, and tetanus hybridoma clones were prepared by this laboratory. The lowest detectable TIG level is 0.05 IU/ml serum instead of 0.1 IU/ml serum. The dose-response curve and cut-off determination system of the new EIA kit are better than those of the original one. We proposed that the newly designed EIA kit could be used for understanding the TIG level in women who are in the age group for giving birth and in the tetanus vaccination group.

Animals↗

Study of specific immune response to unadsorbed concentrated tetanus vaccine administered by intradermal route to non-immunized persons in the last ten years.

Investigations of anti-tetanus response, in 404 subjects, most of them aged 60, being non-immunized for at least 10 years, stressed out the fact that 28.7% were not protected and 6.18% presented a protecting titer of 0.01 IU/ml, evaluated by "in vivo" protection test in mice. Some subjects were immunized with unadsorbed Tetanus vaccine (10 Lf/0.1 ml/dose) by i.d. route, using Jet-injector, and the others with adsorbed Tetanus vaccine (0.5 ml/dose), by i.m. route, using the needle and syringe. The vaccines were well tolerated and adverse reactions were not recorded. After 30 days, a single vaccine dose produced a protecting effect in 97.45% of non-protected subjects, belonging to i.d. immunized group, and also in 93.33% belonging to i.m. immunized group. 30 days after the administration of a second dose, protection set up in all subjects, no matter of vaccine type and administration route used. For a continuous reduction of tetanus morbidity, the authors suggest a specific periodical immunization of non-protected persons, selected by serological screening, using unadsorbed Tetanus vaccine, administered by i.d. route by means of the Jet-injector.

Adsorption↗

[Mortality from tetanus in children less than 1 year of age, Mexico, 1970-1982].

The results of a study about mortality by tetanus in Mexican children under one year of age, during the 1970-1982 period, are reported. This age-group was subdivided in three, as follows: perinatal (less than 7 days), neonatal (less than 29 days) and postneonatal (29 to 364 days). Mortality by tetanus in children under one year of age showed a decreasing trend during the mentioned period, and this was most pronounced from 1979, because of changes in the codification of mortality by tetanus in this group of age. On the other hand, it was found that the greatest proportion of deaths by tetanus happened in the under one year of age group, and particularly in the neonatal group (less than 29 days). The geographic distribution of tetanus in Mexico was studied later, and showed a predominant incidence of the disease in coastal states of the country; an additional finding in this investigation was the displacement of the disease from the Pacific strip to the Gulf of Mexico. Finally, the mortality differentials by sex were studied, and showed that males were the most affected in the three age groups. We cannot explain this finding at the time.

Female↗

Measurement of mortality from neonatal tetanus in Burma.

Surveys to determine mortality from neonatal tetanus were conducted in March and April 1985 in accessible areas of Burma, where pregnant women had been immunized with tetanus toxoid and, for comparison, also in areas where such immunization had not been given. Neonatal mortality rates were three times greater in areas where tetanus toxoid immunization had only recently or had not yet been introduced by the national expanded programme on immunization. Analysis of the data indicates that the impact on reduction of neonatal mortality from tetanus of three interventions (immunization of pregnant women with tetanus toxoid; delivery in hospital; or birth at home attended by a trained health worker) was greatest for immunization.

Health Surveys↗

Tetanus in leprosy patients: report of five cases.

It has long been noted that tetanus is rare in leprosy patients. Five cases of tetanus are reported in leprosy patients in Addis Ababa, Ethiopia. Although natural immunity to tetanus occurs and this appears to be higher in leprosy patients than in the general population, it is not completely protective. Further research on the relationship between tetanus and leprosy is indicated. Although firm epidemiologic data are lacking, it is prudent to give leprosy patients at least one dose of tetanus toxoid.

Adult↗

Defective memory B cell formation in patients with inflammatory bowel disease following tetanus toxoid booster immunization.

Inflammatory bowel disease patients with mild to inactive disease were studied for their ability to generate pokeweed mitogen responsive anti-tetanus toxoid IgG producing B cells in the peripheral blood 21 days following in vivo tetanus toxoid booster immunization. Compared to normals and disease controls, patients with inflammatory bowel disease had significantly impaired in vitro production of anti-tetanus toxoid antibody during an 8 day pokeweed mitogen stimulated culture period. There was poor correlation between the ratio of helper to suppressor T cells in the peripheral blood and pokeweed mitogen stimulated antibody production. Likewise, there was little correlation between in vitro antibody production and peripheral blood natural killer cell cytotoxic activity. Culture of the patients B cells with normal T cells failed to improve antibody production in vitro. These results indicate that many inflammatory bowel disease patients have an impaired humoral immune response to tetanus toxoid booster immunization. This impaired immune response may be due to an inability to generate B cell precursors of anti-tetanus toxoid IgG producing B cells rather than to abnormal circulating helper or suppressor T cell activity or natural killer cell regulatory activity.

Adult↗

In vitro immunization of human lymphocytes. I. Production of human monoclonal antibodies against bombesin and tetanus toxoid.

A procedure for in vitro sensitization of human lymphocytes against bombesin conjugated to tetanus toxoid (BTT) is described. Bombesin is a tetradecapeptide associated with small cell lung carcinoma. We found that antibody responses against bombesin as well as tetanus toxoid could be generated in vitro by culturing nylon-separated human splenic lymphocytes for 6 days with lipopolysaccharide, phytohemagglutinin-activated lymphocyte supernatants, human AB serum, and bombesin conjugated to tetanus toxoid. Cells sensitized by this procedure were fused to murine myeloma cells, NS-1. The specificities of resulting hybrids were analyzed by enzyme-linked immunoassays and competitive inhibition experiments. Hybrids secreting anti-bombesin (IgM) or anti-tetanus toxoid (IgM or IgG) were obtained. The ratio of IgG to IgM antibodies against tetanus toxoid could be increased by using antigen coupled to Sepharose beads. The sensitization procedure described here offers a system for the study of antigenic stimulation of human B lymphocytes in vitro and for the production of human monoclonal antibodies with the desired specificities.

Animals↗

Structure of tetanus toxin. I. Breakdown of the toxin molecule and discrimination between polypeptide fragments.

Tetanus toxin was digested with papain, yielding one major polypeptide (Fragment C) with a molecular weight corresponding to 47,000 +/- 5%, thus comprising about one-third of the toxin molecule. Fragment C was antigenically active, atoxic, and stimulated the formation of antibodies neutralizing the lethal action of tetanus toxin in vivo. Furthermore, a second split product (Fragment B) was isolated from the papain digest, containing two polypeptide chains linked together via a disulfide bond. Fragment B (Mr = 95,000 +/- 5%) was atoxic and showed a reaction of nonidentity with Fragment C on immunodiffusion analysis against tetanus antitoxin. The basic two-chain structure (heavy and light chain polypeptide, cf. Matsuda, M., and Yoneda, M. (1975) Infect. Immun. 12, 1147-1153) of tetanus toxin has been confirmed and the relationship between Fragments B and C within this framework has been established. Fragment C was distinguished from the light chain by electrophoresis in sodium dodecyl sulfate and by immunodiffusion analysis, indicating that this fragment constitutes a portion of the heavy chain polypeptide. Fragment B showed a reaction of partial identity with the light as well as the heavy chain from tetanus toxin. Reduction of Fragment B with dithiothreitol followed by gel chromatography yielded a fraction which was indistinguishable from the light chain portion of the toxin molecule. It is concluded that Fragment B comprises the complementary portion of the heavy chain (remaining after scission of the polypeptide bond(s) releasing Fragment C) linked to the light chain by a disulfide bond.

Amino Acids↗

Geographical distribution of tetanus in the world, 1951-60. A review of the problem.

The introduction of tetanus toxoid about three decades ago, which was followed in many parts of the world by programmes of immunization of the population, has contributed greatly to the control of tetanus in the developed countries. Nevertheless, during the decade 1951-60, tetanus remained an unsolved problem in many of the developing countries.In the present report, it is shown, on the basis of the available literature and WHO statistics, that tetanus causes more than 50 000 deaths each year all over the world. Indeed, this figure should be regarded as an underestimate, since it only partially reflects the actual situation in the developing countries. The paper draws attention to the geographical distribution of tetanus in the world and indicates that existing "foci" or "zones" of infection may be attributed to environmental conditions as well as to social, economic and cultural factors.

Tetanus↗

[Immunity in tetanus].

Among twenty six patients who have got tetanus the movement of the IgG, IgA, IgM, the serum complement, the number of B end T lymphocytes do not change in a significant way during the illness. There is no abnormally that could be considered as a consequence or a favorable factor of tetanus. In a group of patients being vaccinated against tetanus it has been given evidence that the specific antibodies develop much later than in a group of non vaccinated blood givers. Such an abnormal response can be found also in a third group of individuals without tetanus but whose ages in the average are comparable to these of the patients (69 years old). Thus, it seems not to be connected with tetanus itself but with the old ages of the patients.

Aged↗

Immunochemistry of groups A, B, and C meningococcal polysaccharide-tetanus toxoid conjugates.

The successful coupling of the meningococcal groups A, B, and C polysaccharides to tetanus toxoid to yield water soluble conjugates is described. Reactive aldehyde groups were strategically introduced into the terminal residues of the polysaccharides by the controlled periodate oxidation of the native groups B and C polysaccharides and of the group A polysaccharide previously modified by the reduction of its terminal reducing N-acetyl-mannosamine residue. This produced essentially monovalent polysaccharide molecules, which were subsequently covalently linked to tetanus toxoid by means of reductive amination. Although the groups A and C polysaccharides proved to be poor immunogens in rabbits and mice, their tetanus toxoid conjugates produced high levels of polysaccharide-specific antibodies in both animals. By contrast, even in the form of its tetanus toxoid conjugate, the group B polysaccharide failed to elicit homologous polysaccharide-specific antibodies in either animal; a major proportion of the antibodies actually produced had a specificity for the linkage area of the conjugate. This evidence is compatible with the hypothesis of the poor immunogenicity of the group B polysaccharide being structure related. Hyperimmunization of mice with the groups A and C polysaccharide-tetanus toxoid conjugates produced antisera with good bactericidal activity against their respective homologous organisms, and indicated the potential of these conjugates as potential human vaccines.

Aldehydes↗

Descriptive epidemiology of tetanus in the Czech Republic in the period of 1960-1993.

Tetanus represented a serious health problem in the Czech Republic until 1974 with a substantial number of deaths. In the period of 1974 to 1976 a mass vaccination campaign was implemented, covering almost all adult population in both sexes. Since that time the incidence of tetanus has sharply decreased and during recent years only sporadic cases of tetanus were reported. There are some important problems pending, which are to be solved as a part of tetanus surveillance in the country. One of the most important is the occurrence of tetanus cases in fully vaccinated subjects.

Adult↗

The role of transglutaminase in the mechanism of action of tetanus toxin.

Tetanus toxin is a zinc-dependent metalloendoprotease that cleaves synaptobrevin, a polypeptide found in the membranes of synaptic vesicles. This action is thought to account for toxin-induced blockade of transmitter release. However, Facchiano and Luini (Fachiano, F., and Luini, A. (1992) J. Biol Chem. 267, 13267-13271) have proposed that tetanus toxin can stimulate transglutaminase, and Facchiano et al. (Facchiano, F., Benfenati, F., Valtorta, F., and Luini, A. (1993) J. Biol Chem. 268, 4588-4591) have further proposed that the stimulated enzyme produces cross-linking of synapsin. These actions might also account for toxin-induced blockade of exocytosis. Therefore, a series of experiments were performed to evaluate the possibility that tetanus toxin exerts its effects via transglutaminase. The results indicated that clostridial neurotoxins were poor substrates for the cross-linking effects of transglutaminase, and transglutaminase was a poor substrate for the proteolytic actions of tetanus toxin. In addition, at concentrations relevant to blockade of exocytosis, clostridial neurotoxins did not act on intact cells to stimulate transglutaminase, nor did they act on the isolated enzyme to stimulate cross-linking of putrescine and dimethylcasein. When used as competitive inhibitors of endogenous transglutaminase substrates, glycine methyl ester and monodansylcadaverine did not block toxin action. Furthermore, concentrations of calcium that were too low to support transglutaminase activity did not prevent toxin action. The data suggest that stimulation of transglutaminase is not the principal mechanism by which tetanus toxin blocks exocytosis in nerve cells.

Amino Acid Sequence↗

The status of tetanus in the United States: implications for occupational health nurses.

1. Tetanus is a potentially lethal, preventable illness. Tetanus spores exist in all environments. 2. Tetanus occurs in individuals over the age of 50 years who have not maintained decade boosters. 3. Occupational health nurses should assess clients for primary series booster tetanus status during routine health promotion and in association with all wound treatment. 4. Tetanus-diptheria immunization should be used for more complete prophylaxis unless diptheria is contraindicated.

Diagnosis, Differential↗

Inhibition of transmitter release correlates with the proteolytic activity of tetanus toxin and botulinus toxin A in individual cultured synapses of Hirudo medicinalis.

We have studied the effects of tetanus toxin and botulinus toxin A on neurotransmitter release in the Retzius-->P-cell synapse of the leech and exploited the unique properties of this system, which allow for combined physiological and biochemical analyses in single-cell pairs. The sequences of Hirudo medicinalis synaptobrevin and synaptosomal-associated protein of 25 kDa (SNAP-25), deduced by cDNA cloning, are 61 and 55% identical, respectively, to their corresponding mammalian homologs. Whereas Hirudo synaptobrevin is proteolyzed by tetanus toxin, its SNAP-25 isoform is resistant to botulinus toxin A cleavage because of amino acid substitutions within and around the putative cleavage site. In close correlation, microinjection of tetanus toxin into the presynaptic neuron produced a block of transmitter release, whereas botulinus toxin A had no effect on synaptic transmission. Subsequent immunoblotting of single-cell pairs demonstrated directly that the tetanus toxin-mediated block of exocytosis is accompanied by cleavage of synaptobrevin in the injected neuron, resulting in the generation of a detectable C-terminal cleavage product. Immunoblotting also confirmed the resistance of SNAP-25 to botulinus toxin A cleavage in vivo. Using recombinant proteins, we show that the N-terminal fragment of synaptobrevin released by tetanus toxin, but not its C-terminal membrane-anchored cleavage product, participates with syntaxin and SNAP-25 in synaptic SNAP receptor (SNARE) ternary complex formation in Hirudo. Our data demonstrate a direct correlation between the inhibition of transmitter release and the ability of the neurotoxin to proteolyze its target protein and support the view that SNARE ternary complex formation is an important step leading to synaptic vesicle exocytosis.

Amino Acid Sequence↗

Tetanus: a case report.

Tetanus is a rare disease in the United States, with only 40 to 60 cases reported annually. This potentially lethal disease affects unimmunized or partially immunized persons, with the elderly at greatest risk. Tetanus usually follows an injury such as a puncture wound, abrasion, or laceration. The pathogen is an anaerobic, spore-forming, gram-negative, ubiquitous bacillus known as Clostridium tetani. In the vegetative form, it produces a lethal toxin, tetanospasmin, which enters the central nervous system through retrograde axonal transport, resulting in characteristic muscle spasms and tonic contractions. Severe tetanus can cause autonomic instability, respiratory arrest, and cardiac arrest. Patients with tetanus usually require intensive care with dose monitoring and extensive supportive care. Most patients experience full recovery with no signs of neurological sequelae. This case report and discussion illustrate the severity of the disease and the complexity of managing a patient with tetanus.

Aged↗