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Local tetanus in rats; concentration of amino acids as studied in spinal cord segments, spinal roots, and dorsal root ganglia.

1. The effect of tetanus toxin injected into one gastrocnemius muscle on the steady state concentration of several amino acids was investigated in spinal cord half segments, spinal roots and dorsal root ganglia of rats. Care was taken to ensure a symmetrical afferent input to the spinal cord and to localize the segment with the highest concentration of tetanus toxin. 2. In the spinal cord segments containing the highest concentration of tetanus toxin the steady state concentration of glycine was higher on the side of the tetanus than on the contralateral control side. Results obtained after intravenous injection of 14C-glycine do not indicate that the higher concentration of glycine on the side of the tetanus was due to a higher uptake of glycine. 3. The results obtained in the spinal cord contradict previous findings of other authors but lend support to the prevailing concept about the action of tetanus toxin in local and general tetanus.

Amino Acids↗

Measurement of human and mouse anti-tetanus antibodies and isotype analysis by ELISA.

A rapid and sensitive enzyme immunoassay (ELISA) was developed for the quantitation of anti-tetanus antibodies. This technique was used to measure antibody levels in the plasma of immunized donors, in human anti-tetanus IgG preparations and in human and mouse hybridomas producing monoclonal antibodies to tetanus toxoid. The assay was capable of detecting antibody levels as low as 5 X 10(-4) IU/ml. By inclusion of an extra step involving antibodies to mouse Ig isotypes, a sandwich enzyme immunoassay (SEI) was developed which permitted determination of the Ig isotype of mouse anti-tetanus antibodies including tetanus-specific mouse monoclonal antibodies. SEI confirmed Protein A-Sepharose fractionation of mouse ascites fluid containing anti-tetanus antibody. The tetanus toxoid-coated plates have a shelf life of at least 1 year.

Animals↗

Antibody response to accelerated immunisation with diphtheria, tetanus, pertussis vaccine.

From May, 1990, a new schedule of immunisation against diphtheria, tetanus, and pertussis (at 2, 3, and 4 months) replaced the previous more widely spaced schedule. A report that children had lower concentrations of diphtheria and tetanus antibodies a month after an accelerated schedule led us to undertake a controlled study to assess antibody response and the persistence of antibodies a year after immunisation in children receiving vaccine according to widely spaced and accelerated schedules. Concentrations of antibodies to diphtheria and tetanus toxoids and to Bordetella pertussis filamentous haemagglutinin (FHA) were measured by solid-phase radioimmunoassay (SP-RIA). We studied 57 children who received accelerated immunisation at median ages of 11, 16, and 21 weeks and two control cohorts (total n = 82) who received vaccine at median ages of 15, 21, and 45 weeks. 6-8 weeks after the third dose the accelerated-schedule group had lower (p < 0.0001) geometric mean concentrations of antibody to tetanus (0.522 [95% CI 0.383-0.710] vs 3.43 [2.45-4.81] IU/mL), diphtheria (0.266 [0.179-0.396] vs 2.39 [0.616-3.53] IU/mL), and FHA (0.044 [0.030-0.063] vs 0.270 [0.196-0.374] units/mL) than the longer-schedule group. 12 months after the third dose the differences between the groups had narrowed (tetanus 0.197 vs 0.341 IU/mL, p = 0.29; diphtheria 0.100 vs 0.131 IU/mL, p = 0.64; FHA 0.014 vs 0.016 units/mL, p = 0.72). At that time all children had tetanus antibody concentrations above protective levels (0.01 IU/mL); only 2 of 31 in the accelerated-schedule group and 3 of 31 in the longer-schedule group had diphtheria antibody concentrations below the protective level. The use of an accelerated schedule of diphtheria, tetanus, and pertussis vaccination is unlikely to lead to an increase in the proportion of children unprotected against these diseases before the preschool booster.

Antibodies, Bacterial↗

Perceptive bilateral deafness following clinical tetanus to a neonate.

A rare case of bilateral perceptive deafness following clinical tetanus is reported. The patient was a 15-day-old neonate. The clinical tetanus was treated with tetanus antitoxin (human gamma globulins) and penicillin. The exact mechanism of auditory nerve damage associated clinical tetanus and treatment with human tetanus antitoxin and penicillin is still not clearly known. We believe that the damage of the hearing organ can be attributed to the tetanus toxin and not to the human gamma globulins (tetanus antitoxin).

Audiometry, Pure-Tone↗

The management and prevention of tetanus.

Tetanus is a rare disease in the United States, but it has a high mortality rate and is preventable through immunization. Using a computerized literature search, we reviewed English language articles on tetanus in the United States. We found that despite the availability of an effective vaccine, tetanus still causes considerable morbidity. The elderly are at great risk of tetanus, because they have never been immunized or their immunity has waned. Emergency physicians can reduce the likelihood of tetanus by ensuring appropriate wound care, including tetanus immunization and use of tetanus immune globulin, as appropriate. Treatment consists of neutralization of circulating toxin, surgical excision to eliminate the source of toxin, control of muscle spasms, and prevention of respiratory and metabolic complications. A case-finding approach for all persons who receive care in emergency departments will reduce the size of the susceptible population.

Adult↗

The effect of reconstitution of an Haemophilus influenzae type b-tentanus toxoid conjugate (PRP-T) vaccine on the immune responses to a diphtheria-tetanus-whole cell pertussis (DTwP) vaccine: a five-year follow-up.

Controversial results have been obtained from previous studies on the combined administration of Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-whole-cell pertussis (DTwP) combination vaccines, with regard to possible reciprocal interference between the constituent antigens. To document the priming effect and possible long-term immunogenic interference of PRP-T and DTwP combination vaccines, a randomized, double-blind, controlled study was conducted in Belgium. A total of 168 healthy infants received, at 3, 4 and 5 months of age, DTwP vaccine mixed just prior to injection either with PRP-T vaccine (group A, DTwP//PRP-T, N = 85) or with placebo (group B, DTwP//Placebo, N = 83). At the age of 14 months, children of both groups were randomized to receive either a dose of DTwP//PRP-T vaccine (subgroups A1 and B1) or a dose of Hib polysaccharide (PRP) vaccine (subgroups A2 and B2). Those children in subgroups A1 and B1 had an additional serum sample taken at the age of 5 years (at the time of a DT booster). The immune response to Hib polysaccharide at the age of 4, 5 and 6 months confirmed the excellent immunogenicity profile of PRP-T in infants. In addition, the vigorous anamnestic response (i.e. a 20-fold increase of GMT) to a booster dose of the plain capsular polysaccharide (PRP) reflected the efficient Hib-priming induced by the combined DTwP//PRP-T vaccine. Reconstitution of PRP-T with DTwP did not affect the immune response to diphtheria toxoid or pertussis agglutinins. Nevertheless, at almost any time point during the five-year follow-up, the tetanus antitoxin GMT values were significantly lower in the DTwP//PRP-T group (A and A1) than in the DTwP//Placebo group (B and B1). Despite the suppressive effect on GMT values, intergroup differences in rates of seroprotection were never significant, except after doses 2 and 3 for which there were lower percentages of children in group A with antitoxin titers > 0.05 IU/mL and > 1.0 IU/mL. In the group primed with the combined DTwP//PRP-T vaccine, (1) a DT booster dose at the age of 5 years provoked a 150-fold increase in tetanus antitoxin GMT, (2) a high tetanus antitoxin GMT value was attained (GMT = 19.3 IU/mL) and (3) all children in this group had tetanus antitoxin titers > 1.0 IU/mL, so it may be concluded that all these children will still be protected against tetanus until at least the age of the next recommended booster dose (i.e. the age of 15 years). No differences in the occurrence of adverse events were observed between the groups who received the DTwP//PRP-T vaccine or the DTwP//Placebo vaccine, both vaccines being associated with events customarily attributable to DTwP (data not shown). Our results indicate (1) that the combination vaccine, DTwP//PRP-T, represents a safe and effective alternative for the existing uncombined vaccines and (2) that the long-term effect of interference between the components of future combination vaccines should be studied with subsequent booster doses, followed by the evaluation of persistence of antibodies over several years.

Agglutination Tests↗

Fatal tetanus in a drug abuser with "protective" antitetanus antibodies.

Tetanus is a rare disease in the United States. From 1995-1997, the average annual incidence of tetanus was 0.15/1,000,000 population. Injecting-drug users, particularly those who use heroin, are among the highest risk population for acquiring tetanus. We present a case of an injecting-drug user who was seen in the emergency department with worsening diffuse midthoracic back pain and spasms. He subsequently developed acute respiratory failure and central nervous system hypoxic injury. Serum obtained before administration of tetanus immune globulin showed a tetanus antibody titer greater than 16 times the level considered protective. Because of limited human data on the minimum protective level of neutralizing antibody, as well as reports of tetanus among individuals with "protective" antibody titers, the diagnosis of tetanus should not be excluded solely on the basis of antitetanus titers.

Antibodies, Bacterial↗

Tetanus in England and Wales, 1984-2000.

A review of national tetanus surveillance in England and Wales during 1984-2000 was undertaken to evaluate the surveillance system and national vaccination policy. Hospital Episode Statistics for tetanus in England for fiscal years 1989/90-1995/6 were also examined to estimate under-reporting. A total of 175 cases of tetanus were reported, giving an annual incidence of 0.20 per million, the lowest levels ever recorded. The highest incidence was in those aged over 64 years (0.66 per million) with no significant sex difference. Twenty (11%) cases were reported in people who were eligible for routine childhood vaccination. Outdoor injuries were the commonest reported exposure risk. Tetanus case under-reporting was estimated as 54-64%. We conclude that GPs should ensure that all their patients are fully vaccinated, targeting those born before 1961. High childhood tetanus vaccination coverage remains a priority. As the disease becomes rarer, enhanced tetanus case surveillance is essential for tetanus immunization policy evaluation.

Adolescent↗

Serological survey of immunity to tetanus in adult population of Northern Halkidiki, Greece.

BACKGROUND: Despite the implementation of the obligatory anti-tetanus vaccination, the tetanus cases in Greece are not eliminated. Because of the increased possibility of Clostridium tetani infection of the Northern Halkidiki population--like any other rural population the evaluation of the immunity to tetanus in the area is considered necessary. METHODS: The tetanus antitoxin levels were determined using the enzyme-linked immunosorbent assay (ELISA) in 405 healthy adult individuals attending the health center for routine laboratory tests. RESULTS: 64.4% of the studied population was found protected (tetanus antitoxin levels > or = 0.1 IU/ml). The percentage of protected people decreased as age increased from 83.3% in the 21-30 to 51.2% in the > 60 age group. 82.1% of the tested males and 52.6% of the tested females had tetanus antitoxin levels > or = 0.1 IU/ml (p < 0.0001). The percentages of immune men (100-66.2% in various age groups) were found higher than those of women (80.8-35.5% in the respective age groups). The geometrical mean titres (GMTs) were 0.44 in all of 261 immune people, 0.53 in 133 immune men and 0.37 in 128 immune women (p = 0.0021). CONCLUSION: The proportion of protection among men over 60 and women over 30 years old is inadequate, the levels of tetanus antitoxin decline with age and a significant difference was found between the proportion of protection of males and females.

Adult↗

A population-based serologic survey of immunity to tetanus in the United States.

BACKGROUND: Vaccination rates are frequently considered a surrogate measure of protection. To provide more accurate estimates, serum levels of antibody against tetanus were measured as part of the third National Health and Nutrition Examination Survey (NHANES III), which studied a representative sample of the civilian, noninstitutionalized population of the United States. METHODS: We measured tetanus antitoxin using a solid-phase enzyme immunoassay in serum samples from 10,618 persons six years of age and older who were examined during phase 1 of NHANES III in 1988 to 1991. RESULTS: Overall, 69.7 percent of Americans six years of age and older had protective levels of tetanus antibodies (> 0.15 IU per milliliter). The rate decreased from 87.7 percent among those 6 to 11 years of age to 27.8 percent among those 70 years of age or older. Among children 6 to 16 years of age, 82.2 percent had protective levels of tetanus antibodies, with little variation according to race or ethnicity. More men than women were immune (79.0 percent vs. 62.4 percent). Mexican Americans had a significantly lower rate of immunity (57.9 percent, P < 0.05) than either non-Hispanic whites (72.7 percent) or non-Hispanic blacks (68.1 percent). Those with a history of military service, higher levels of education, or incomes above the poverty level were more likely to have protective antibody levels. Although the prevalence of immunity declined rapidly starting at the age of 40 years, most of the 107 cases of tetanus (with 20 deaths) reported in 1989 and 1990 occurred in persons 60 years of age or older. CONCLUSIONS: Despite the fact that effective vaccines against tetanus have been available since the 1940s, many Americans do not have immunity to tetanus, and the rates are lowest among the elderly. There is an excellent correlation between vaccination rates (96 percent) and immunity (96 percent) among six-year-olds. However, antibody levels decline over time, and one fifth of older children (10 to 16 years of age) do not have protective antibody levels.

Adolescent↗

Tetanus immunity in elderly people.

The aims of this study were to document the level of tetanus immunity in elderly people; to assess the value of immunization history in predicting tetanus immune status and to determine the response to tetanus immunization in elderly people compared with younger subjects. One-hundred day-hospital attenders (group 1), 100 long-term-care residents (group 2) and 50 young subjects (group 3) were recruited. Protective titres of tetanus antitoxin antibodies were detected in 20% of group 1, 45% of group 2 and 80% of group 3. Tetanus immunization history was a poor predictor of immune status in older people with a positive predictive value of 50% and a negative predictive value of 76%. The response to tetanus immunization was slower and of lower magnitude in older people. However, 36 of 37 older subjects developed protective levels of tetanus antitoxin antibodies on completion of a primary immunization programme.

Adult↗

Naturally acquired antibodies to tetanus toxin in humans and animals from the galápagos islands.

A serologic survey using a highly sensitive enzyme-linked immunosorbent assay confirmed the anticipated finding of naturally acquired antibodies to tetanus toxin both in humans and animals on the Galápagos Islands. In 57 inhabitants (mean age, 31.3 years) who had not been vaccinated against tetanus, antibody to tetanus toxin was detected in the blood in varying titers (geometric mean [reciprocal] titer [GMT], 0.015 international units [IU]/ml). In one individual the titer of antibody was greater than 12.5 IU/ml. Two individuals who had never been vaccinated against tetanus but who had reported having had clinical tetanus had titers of antibody to tetanus toxin of 0.02 IU/ml and 0.3 IU/ml, respectively. All nine of the animals studied showed antibody to tetanus toxin (GMT, 0.028 IU/ml).

Adolescent↗

Antibodies against the light chain of tetanus toxin in human sera.

Tetanus toxoid elicits protective antibodies against tetanus toxin in humans and animals. It has been reported that antitoxin from immunized humans contains no anti-light chain antibodies, based on immunodiffusion and quantitative precipitin analyses. We confirmed the absence of precipitating anti-light chain antibodies in tetanus immune globulin. However, the presence of antibodies against the light chain of the toxin was shown by direct binding and inhibition analyses, using enzyme-linked immunosorbent assays. Using a neutralization inhibition test, we also found that about one-fourth of the neutralizing antibodies in tetanus immune globulin are directed against the light chain. These results suggest that the light chain of tetanus toxin contains immunogenic determinants and that antibodies directed against it may have a role in the prevention of tetanus or treatment of tetanus or both.

Antibody Specificity↗

Effect of a single tetanus-diphtheria vaccine dose on the immunity of elderly people in São Paulo, Brazil.

Epidemiological data regarding tetanus and diphtheria immunity in elderly people in Brazil are scarce. During the First National Immunization Campaign for the Elderly in Brazil in April 1999, 98 individuals (median age: 84 years) received one tetanus-dyphtheria (Td) vaccine dose (Butantan Institute, lot number 9808079/G). Inclusion criteria were elderly individuals without a history of severe immunosuppressive disease, acute infectious disease or use of immunomodulators. Blood samples were collected immediately before the vaccine and 30 days later. Serum was separated and stored at -20 degrees C until analysis. Tetanus and diphtheria antibodies were measured by the double-antigen ELISA test. Tetanus and diphtheria antibody concentrations lower than 0.01 IU/mL were considered to indicate the absence of protection, between 0.01 and 0.09 IU/mL were considered to indicate basic immunity, and values of 0.1 IU/mL or higher were considered to indicate full protection. Before vaccination, 18% of the individuals were susceptible to diphtheria and 94% were susceptible to tetanus. After one Td dose, 78% became fully immune to diphtheria, 13% attained basic immunity, and 9% were still susceptible to the disease. In contrast, 79% remained susceptible to tetanus, 4% had basic immunity and 17% were fully immune. Although one Td dose increases immunity to diphtheria in many elderly people who live in Brazil, a complete vaccination series appears to be necessary for the prevention of tetanus.

Aged↗

Immunity to tetanus in male adults in Dar es Salaam, Tanzania.

OBJECTIVE: To determine immunity to tetanus in male blood donors with previous diphtheria-pertussis-tetanus (DPT)/tetanus toxoid (TT) vaccination. DESIGN: A cross sectional study, conducted in September 1999. SETTING: Blood bank, Muhimbili Medical Centre, Dar es Salaam, Tanzania. METHODS: Using an antigen competition ELISA technique, serum tetanus anti-toxin levels in two hundred male blood donors were determined. RESULTS: Vaccination history was absent in 43 (21.5%) blood donors, whereas 60 (30%) and 97 (48.5%) reported childhood DPT and TT vaccination, respectively. Tetanus anti-toxin was undetectable in 47 (23.5%) blood donors and the levels were below that considered protective (> or = 0.1 IU/ml) in 25 (12.5%). Among those with undetectable level, 43 (91.5%) had no vaccination history. Time after last DPT/TT vaccination correlated significantly with tetanus anti-toxin levels (r2=-0.331, p=0.001). In multivariate analysis, TT doses received and time after last vaccination explained 4.8% and 29.4%, respectively, of the variations in tetanus anti-toxin levels. CONCLUSION: Seventy two (36%) male blood donors were susceptible to tetanus and the susceptibility was highest from 48 years. A regular TT booster dose at 10 yearly intervals is recommended to provide adequate and long lasting immunity in male adults. Proper keeping of vaccination records is emphasised.

Adolescent↗

Immunity to diphtheria and tetanus in Australia: a national serosurvey.

OBJECTIVE: To determine immunity to tetanus and diphtheria in the Australian population. DESIGN AND SETTING: Analysis, using double antigen enzyme immunoassays, of a representative sample of sera (1950 samples tested for diphtheria and 2884 for tetanus) collected opportunistically from Australian laboratories between July 1996 and May 1999. MAIN OUTCOME MEASURE: Immunity to diphtheria and tetanus, defined as negative (susceptible) when the antitoxin level was < 0.01 IU/mL, positive (immune) when it was > or = 0.1 IU/mL, and low positive (partially immune) when it was in the range 0.01-< 0.1 IU/mL. RESULTS: About 99% of children aged 5-9 years had diphtheria and tetanus antitoxin levels > or = 0.01 IU/mL (immune or partially immune). Antitoxin levels declined with age and generally more markedly for diphtheria than tetanus. For subjects aged 50 years and over, less than 60% were immune or partially immune to diphtheria and less than 75% to tetanus. Men and women had similar diphtheria antitoxin levels, while women had lower levels of tetanus antitoxin compared with men of the same age, with the difference being most marked in the age group > or = 70 years (37% v 60%; P < 0.001). CONCLUSIONS: Immunity in children appears to be good, but adults, especially older people, may not be adequately protected. Recent changes to the Australian Standard Vaccination Schedule should improve immunity in cohorts now aged < 50 years. However, additional efforts are required to protect those over 50 years (especially travellers), who are most susceptible.

Adolescent↗

Tetanus. A clinical review.

OBJECTIVE: Although tetanus is now uncommon in Oman (The Expanded Program on Immunization was introduced in 1981), patients continue to present from time to time at an average rate of 6 cases per year. Worldwide, the mortality rate for tetanus remains high (ranging from 15-20% in developed countries). At the Sultan Qaboos University Hospital, Muscat, Oman, prolonged Intensive Care Unit treatment and multi-disciplinary management is invariably required for tetanus patients. This study was carried out to evaluate our results over the past decade. METHODS: All tetanus patients admitted to the Sultan Qaboos University Hospital from 1991 up to the end of 1999 were retrospectively reviewed. Patients were diagnosed early, and aggressive treatment in the Intensive Care Unit was instituted, with a coordinated multidisciplinary management. RESULTS: Ten cases were identified and included in the review, comprising 9 adults and one infant aged 2 weeks. Adult patients were aged 36-75 years (mean 59 years), and the average Intensive Care Unit stay of the 9 surviving patients was 5.5 weeks (range 3-7 weeks). All patients presented with severe generalized tetanus. Two patients with traditional cautery marks developed tetanus. A focus of infection could not be found in 2 patients. All patients had early tracheostomy and assisted ventilation with appropriate sedation. One patient required almost 45 gm of diazepam throughout his Intensive Care Unit stay. One adult patient died on the 6th day of admission following myocardial infarction. The neonatal case survived after 35 days care in the Intensive Care Unit. The mortality rate for our patients was therefore 10%. CONCLUSION: Tetanus in Oman remains an infrequent but important disease requiring costly and prolonged Intensive Care Unit treatment. We attribute the comparatively low mortality rate (10%) in this study, to early diagnosis, institution of aggressive treatment, good nursing as well as a well-coordinated multi-disciplinary management.

Adult↗

[Localized tetanus in Abidjan: clinical and prognostic features (1976-1997)].

UNLABELLED: Localised tetanus, rarely described in Africa, was examined retrospectively in Abidjan, over a period of 22 years (1976-97). Forty-five patients--representing an incidence rate of 2% of tetanus cases--were reported in this time span. The mean age was 23 years, and none of the patients had had prior access to adequate immunoprophylaxis. Three clinical forms were observed: tetanus of the limbs (32 cases, 71%), cephalic tetanus (11 cases, 25%), and abdominal tetanus (2 cases, 4%). Infection had occurred via wounds of the limbs (38%), intramuscular injections (33%), craniofacial wounds (25%), and abdominal wounds (2%). No portal of entry was identified for 2% of the cases. 37 patients were cured (82%) of whom 5 retained sequelae (11%). 7 deaths were observed (16%). In terms of prognosis, the only risk was secondary generalisation of tetanus (27%). CONCLUSION: Localised tetanus is far from being mild and incurs significant rates of sequelae. The only efficient treatment is immunisation-based prophylaxis.

Adolescent↗