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Tetanus and diphtheria immunity among females in the United States: are recommendations being followed?

OBJECTIVE: The purpose of this study was to examine prevalence and factors associated with tetanus and diphtheria immunity among women in the United States. STUDY DESIGN: Sera from 9411 female participants from the third National Health and Nutrition Examination Survey were tested for diphtheria and tetanus antitoxin. Interview information for adult women was analyzed to examine associations with immunity. RESULTS: Fifty-seven percent of the female subjects who were > or =6 years old were positive for diphtheria, and 64% of the female subjects for tetanus anti-toxin. Among women > or =20 years old, only 41% of the women were protected against both antigens. Older age, birth outside the United States, and less education was associated with lower immunity. Markers for contact with the health care system were not related to higher immunity. CONCLUSION: More than one half of US women > or =20 years old who were tested were not protected fully against diphtheria and tetanus. All physicians, including obstetricians and gynecologists who may be the sole medical providers for women, should be familiar with the current Advisory Committee on Immunization Practices recommendations regarding tetanus and diphtheria toxoid booster vaccines.

Adolescent↗

Neonatal tetanus: a continuing challenge in the southeast of Turkey: risk factors, clinical features and prognostic factors.

Neonatal tetanus (NT) still causes significant mortality in developing countries, although in 1989 WHO adopted the goal of eliminating the disease by 1995-2000. To characterize the regional characteristics, clinical charts of 55 neonates (42 males and 13 females) admitted to the Pediatric Infectious Diseases Ward of Dicle University Hospital, Diyarbakir, Turkey with the diagnosis of NT from 1991 to 1997 were reviewed. Mean age at admittance was 8.9+/-4.3 days with a range of 3-25 days. Mean period for the appearance of first symptoms was 5.8 days ranging between 1 and 21 days. Mean birth weight of the patients was 3369+/-560g. All patients were from rural areas and were delivered at home by untrained traditional birth attendants with no prior antenatal healthcare services. Razor blade (55%), scissors (27%), and knife (18%) were the instruments used to cut the cord in non-hygienic conditions. No mothers had prior vaccination with tetanus toxoid during their pregnancy. Spasticity (76%), lack of sucking (71%), trismus (60%), fever (49%), omphalitis (44%), irritability (24%), risus sardonicus (22%), and opithotonus (15%) were the most common presenting signs and symptoms. Age at admission < 7.5 days and symptoms of onset <4.9 days, risus sardonicus and opisthotonus were associated with fatal outcome. All patients were treated with human tetanus immunglobulin or equine tetanus antitoxin where available, antibiotic therapy by penicillin G (100.000 U/kg/day) and intravenous high dose diazepam (40 mg/kg/day). Overall mortality rate was 40% (22 cases), without any equipment for mechanical ventilation. Health education of mothers and birth attendants, promotion of hospital delivery and prenatal tetanus immunization of all pregnant women particularly in rural areas are recommended, if NT is to be prevented.

Adult↗

Quantification of tetanus antitoxin in human sera. I. Counter-immunoelectrophoresis.

An extensive sero-epidemiological survey of immunity to tetanus is to be performed in Norway during 1978 and 1979 and thus a simple and reliable method for screening sera for content of tetanus antitoxin is needed. An improved counter-immunoelectrophoretic method for quantification of tetanus antitoxin is described. The toxin neutralization test in mice is considered to correlate well with protection in humans. Counter-immunoelectrophoresis has the advantage of using tetanus toxoid instead of toxin as well as being more rapid and less expensive. Specific antibodies of the IgG, IgM, and IgA classes could be read simultaneously for many sera. This may be of importance, since it is reported in the literature that only antibody of the IgG class is capable of neutralizing tetanus toxin in mice. Counter-immunoelectrophoresis is limited by being less sensitive than the toxin neutralization test in mice.

Chromatography, Gel↗

Combined active-passive immunisation of horses against tetanus.

The protection afforded by active, passive and combined active-passive methods of immunisation against tetanus was examined in previously unimmunised horses. Three groups of horses were injected; one with tetanus toxoid alone, one with tetanus antitoxin alone and one in which the tetanus toxoid and tetanus antitoxin were injected simultaneously. The protection afforded was determined by monitoring the levels of antitoxin achieved in the horses by each of these methods. The results obtained demonstrated the effectiveness of the combined active-passive method in affording rapid and prolonged protection and enabled the examination of some of the factors involved in active and in passive immunisation when used alone. The advantages obtained by the use of the combined active-passive method in protecting unimmunised horses suddenly placed at risk to infection are outlined.

Animals↗

Acellular pertussis vaccine booster combined with diphtheria and tetanus toxoids for adolescents.

BACKGROUND: The incidence of pertussis is increasing, especially in adolescents, attributed in part to waning of immunity after childhood immunization. Recently licensed in the United States for use in adolescents, acellular pertussis vaccines will provide an immunogenic and safe option for booster immunization against pertussis. METHODS: This prospective, randomized, observer-blinded, multicenter, comparative study evaluated the safety and immunogenicity of a vaccine formulated with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis antigens (Tdap) compared with tetanus and diphtheria toxoids vaccine (Td) for booster immunization in adolescents. There were 4114 healthy adolescents aged 10 to 18 years who completed childhood vaccination against diphtheria, tetanus, and pertussis who were enrolled, randomized, and received study vaccine. RESULTS: Local and general symptoms were comparable between the Tdap and Td groups. The immune response of Tdap was comparable with Td vaccine for tetanus and diphtheria seroprotection and booster responses. In addition, geometric mean concentrations of antibody to pertussis antigens, pertussis toxoid, filamentous hemagglutinin, and pertactin exceeded the antibody response elicited after infant immunization with diphtheria and tetanus toxoids and acellular pertussis antigens (DTaP) that had proven efficacy against pertussis. CONCLUSIONS: In adolescents, the studied Tdap was safe and immunogenic and induced pertussis antibodies that were higher than those associated with efficacy in infants.

Adolescent↗

[Development of a numerically additive combined vaccine against tetanus and smallpox].

Mandatory vaccination against smallpox was abolished on the account of smallpox-eradication proclaimed by the WHO and the postvaccinal complications detected after smallpox vaccination. At the same time vaccine banks with the vaccinia virus strain "Elstree" were organized. Should mass vaccinations with this vaccinia virus strain be carried out in a case of emergency, severe postvaccinal diseases and complications can arise in overaged and immunosuppressed vaccinees after primovaccination. Therefore attenuated vaccinia virus strains should be used for vaccine banks, which cannot be activated, or increase in virulence in impaired vaccinees after primovaccination. For these individuals the vaccinia virus strain "MVA", among other attenuated vaccinia strains, is recommended. The MVA virus strain can be applied parenterally without complications. From the scientific and field-relevant point of view it was tried to combine the vaccinia virus strain "MVA" with tetanus toxoid and to develop a combination vaccine "tetanus-smallpox". In immunization experiments using mice, piglets and monkeys, safety and efficacy of the vaccine were investigated. Efficacy was demonstrated by means of postvaccinal antibody determination and by the mouse protection test. Tetanus antitoxin was measured by ELISA and indirect hemagglutination test, antibody levels to vaccinia virus were investigated employing the neutralization test and hemagglutination inhibition test. No significant differences in potency could be demonstrated between the combination vaccine and the corresponding monovalent vaccines in mice, piglets and monkeys. The combination vaccine consisted of 12 Lf tetanus toxoid and 10 TCID50 vaccinia virus "MVA" preserved with gelatine and glucosamine. The double intramuscular immunization of monkeys stimulated average tetanus antitoxin titers of 1:310 and average vaccinia virus titers of 1:195 2 weeks p. revacc. Similar results were obtained in mice and piglets. Side reactions were not observed in mice and piglets. Except for occasional local reactions of short duration at the injection site of the monkeys, similarly no adverse reactions were observed after intramuscular vaccination with the combination vaccine.

Adjuvants, Immunologic↗

Combined active-passive immunization against tetanus in man.

A schedule for the prevention of tetanus in the injured, which has been in operation in the emergency department of a large hospital for over two years, is proposed. For the majority of nonimmunized persons, it is recommended that a dose of toxoid and 50 units tetanus immune globulin (human) (TIGH) be given, in separate sites, to be followed later by additional doses of toxoid for the completion of active immunization. Combined active-passive immunization with tetanus toxoid and 50 units TIGH gives a low level of passive immunity and stimulates early onset of active immunization. In combined active-passive immunization, adsorbed tetanus toxoid produced a significantly higher response than the fluid toxoid. The injection of 400 units TIGH somewhat suppressed the induction of immunity following the first dose of AlPO(4)-tetanus toxoid.

Antibody Formation↗

Tetanus.

Tetanus results from the action of a powerful exotoxin produced by Clostridium tetani. It can be prevented only by active and passive immunization procedures. The vaccine is one of the safest and most effective vaccines ever developed, and is capable of inducing long term protection in individual vaccinees. Adequate immunization before, or during pregnancy can eliminate the risk of neonatal tetanus in infants born in developing countries. In non-immune patients, tetanus prophylaxis requires the use of tetanus immunoglobulin, or tetanus antiserum in addition to adequate wound care.

Humans↗

[Tetanus in Libreville: hospital analysis of 30 cases].

We investigated 34 cases of tetanus in patients younger than 75 years old in Libreville. We found that the incidence of tetanus was 8 cases for every million people. The disease mostly affected people younger than 50 (85%). Only two neonatal tetanus cases were reported. The death rate was 74%, despite the availability of intensive care and respiratory assistance. We stress the benefits of tetanus immunization, which must be continued, and suggest the use of intrathecal serotherapy for the cure of tetanus in Libreville.

Adolescent↗

Oral immunization against tetanus.

Model experiments in mice were used for the investigation of oral immunization against tetanus. The efficacy of oral tetanus toxoid application was tested by subcutaneous challenge (10 LD50 tetanus toxin) and antitoxin determination by L+-method. Reasonable protection could only be achieved when toxoid was in intensive contact with the mucous membranes of the oral cavity, whereas immunization by way of the gastrointestinal tract failed completely. After a single oral vaccination with 200 Lf fluid tetanus toxoid onto mucous membranes of the oral cavity the efficiency index was 75. A 100% protection was obtained in challenge after 3 applications of 200 Lf toxoid. In comparison, a single subcutaneous dose of 2 Lf tetanus toxoid resulted in an efficiency index of 100 and a single intranasal immunization with 100 Lf in an efficiency index of 93. Development of immunity after oral immunization was much accelerated if compared with parenteral immunization. 20% of the orally treated animals were immune 5 days after vaccination. After the same period subcutaneously treated animals had failed to develop any protection at all. Antitoxin titers after one oral vaccination (200 Lf) were similar to the ones after one subcutaneous dose (2 Lf). A distinct increase in antitoxin titers could only be observed when revaccination was done subcutaneously. The results obtained with mice apply analogically to guinea pigs.

Administration, Intranasal↗

Induction of LTP in rat primary visual cortex: tetanus parameters.

Long-term potentiation (LTP), intensively studied in the hippocampus as a possible mnemonic device, has begun to be studied in the neocortex. In this study the effects of varying tetanic stimulus parameters on LTP of field potentials recorded from layer II/III induced by white matter stimulation in the in vitro rat visual cortical slice were examined. Low intensity tetanus was more effective in producing LTP than high-intensity tetanus, although single pulses of very high intensity reliably resulted in LTP. LTP consistently occurred following 2 Hz-60 min, or 100 Hz-10 min tetanus; whereas, 10 min of 7 and 25 Hz tetanus usually resulted in long-lasting depression. Although no obvious rule related tetanus frequency and duration to the incidence of LTP, an inverted-U relationship was found between tetanus frequency and LTP magnitude.

Animals↗

Reversal of long-term potentiation (depotentiation) induced by tetanus stimulation of the input to CA1 neurons of guinea pig hippocampal slices.

The reduction of the long-term potentiated response induced by tetanus (depotentiation (DP) of LTP) was investigated by the delivery of a train of low-frequency afferent stimuli (depotentiating stimulation: DPS) after the tetanus (100 Hz, 100 pulses) in CA1 neurons of the guinea pig's hippocampal slice. The parameters of DPS (frequencies of 1, 2, 5 and 10 Hz; number of pulses of 200 and 1000; and the time-lag after tetanus of 20 and 100 min) were altered systematically and their effects on LTP were evaluated through the analysis of the slope of field EPSP (S-EPSP) and amplitude and peak latency of population spike (A- and L-PS). DPS of 1 Hz, 1000 pulses, given 20 min after tetanus, reduced the potentiated component of S-EPSP, A-PS and L-PS by 68.5%, 80.1% and 56.1%, respectively (mean, n = 6), whereas it reduced the control response by 4.3%, 7.1%, and 1.9%, respectively (n = 6). Significantly less effectiveness was observed for DPS at higher frequencies (2-10 Hz), with smaller numbers of pulses, featuring a longer time-lag after tetanus and under APV administration. When DPS was applied before tetanus, significantly less robust LTP was observed. However, these effects were blocked by the administration of APV during DPS.

2-Amino-5-phosphonovalerate↗

Changes in the paired-pulse ratio after long-term potentiation induced by 2- and 100-Hz tetanus in rat visual cortical slices.

The effects of 2- and 100-Hz tetanus on long-term potentiation (LTP) of field potentials recorded from layers II/III and induced in layer IV in rat visual cortical slices were examined. Paired-pulse stimulation was used to probe the different mechanisms of LTP induced by 2- and 100-Hz tetanus. The paired-pulse ratio (PPR) decreased after the LTP induced by 2-Hz tetanus, with the changes in PPR being correlated with LTP amplitude. However, in the LTP induced by 100-Hz tetanus, the changes in PPR were not correlated with LTP expression. These experiments suggest that an enhanced probability of presynaptic transmitter release underlies LTP induced by 2-Hz tetanus, but not LTP induced by 100-Hz tetanus.

Animals↗

[Diphtheria and tetanus antibodies in children and young adults (author's transl)].

Diphtheria and tetanus antibodies were determined in a random sample of 635 test persons of 1 to 25 years of age via the passive haemagglutination test. Using sera and immunoglobulins standardized for protective capacity, titres were expressed as international units (IU). Titres greater than or equal to 0.01 IU/ml diphtheria antitoxin were detected in 96% of children (1-17 years, n = 70), in 79% of adults aged 18-22 (n = 397), in 68% of adults aged 23-25 (n = 168); tetanus antitoxin was found in 96% of children and 90% of adults. 9% of the males between 18 and 22 years of age had no detectable tetanus antibodies before of the same age had no tetanus antibodies. Safe protection (greater than or equal to 0.1 IU/ml) against diphtheria may be expected in 56% of children and in 35% of adults only, against tetanus in 86% and 75%, respectively. 25% of all test persons had excessive tetanus titres (greater than or equal to 10 IU/ml).

Adolescent↗

Tetanus relaxation of fast skeletal muscles of the mouse made parvalbumin deficient by gene inactivation.

The effects of tetanus duration on the relaxation rate of extensor digitorum longus (EDL) and flexor digitorum brevis (FDB) muscles were studied in normal (wild-type, WT) and parvalbumin-deficient (PVKO) mice, at 20 C. In EDL of PVKO, the relaxation rate was low and unaffected by tetanus duration (< 3.2 s). In contrast, the relaxation rate of WT muscles decreased when tetanus duration increased from 0.2 to 3.2 s. In WT muscles, fast relaxation recovered as the rest interval increased. Specific effect of parvalbumin was asserted by calculating the difference in relaxation rate between WT and PVKO muscles. For EDL, the rate constant of relaxation slowing was 1.10 s-1 of tetanization; the rate constant of relaxation recovery was 0.05 s-1 of rest. In FDB, the effects of tetanus duration on WT and PVKO muscles were qualitatively similar to those observed in EDL. Relaxation slowing as tetanus duration increases, reflects the progressive saturation of parvalbumin by Ca2+, while recovery as rest interval increases reflects the return to Ca2+-free parvalbumin. At all tetanus durations, relaxation rate still remained slightly faster in WT muscles. This suggested that parvalbumin facilitates calcium traffic from myofibrils to the SR. No difference was found between WT and PVKO muscles for: (i) the expression of the fast isoforms of myosin heavy chains, (ii) the force-velocity relationship and maximal shortening velocity and (iii) the Ca2+-activated ATPase activity from isolated preparations of the sarcoplasmic reticulum (SR).

Animals↗

The effect of dantrolene on the enhancement and diminution of tension evoked by staircase and by tetanus in rat muscle.

1. The effect of Dantrolene on the potentiation of isometric twitch tension was examined during and after the staircase (5/sec, 250 stimuli) and after the tetanus (167/sec, 250 stimuli) in the extensor digitorum longus muscle of adult Lewis rats at 37-38 degrees C.2. The study confirmed that Dantrolene decreased the twitch tension much more than the tetanic tension. The drug shortened the contraction time of the twitch. The rate of force development of the twitch was diminished by only half that of the twitch tension. The findings may suggest that the drug both shortened and diminished the activation of the muscle during the twitch.3. Dantrolene decreased the potentiation produced by a given number of stimuli early in the staircase. At the 250th stimulus the staircase was about 25% larger after than before application of the drug. Dantrolene increased the potentiation 2 sec after the tetanus by about 60%.4. After application of Dantrolene, the decay of potentiation after the staircase indicated that the process that diminished the twitch during the staircase, present before application of the drug, was absent. The size of the process causing potentiation was the same with and without the drug. Both events of potentiation after the tetanus were increased by Dantrolene. Both after the staircase and after the tetanus, Dantrolene increased the slow phase of decay by 60-70%. The fast rate of decay after the tetanus was unchanged by the drug.5. The contraction time was prolonged less in the potentiated twitch after than before application of Dantrolene. This was presumably due to a greater relative increase in activation rather than to a prolongation of the time during which the muscle was activated.6. A model is proposed where the delay in potentiation during the staircase and the increase in potentiation after the tetanus are due to the proportion of sites in the excitation-contraction coupling occupied by Dantrolene being reduced by repetitive depolarizations of the transverse tubules during trains of repetitive stimuli.

Action Potentials↗

Comparative analysis of tetanus antitoxin titers of sera from immunized mice and guinea pigs determined by toxin neutralization test and enzyme-linked immunosorbent assay.

Enzyme-linked immunosorbent assay (ELISA) and toxin neutralization (TN) test were comparatively evaluated for determination of antibodies to tetanus toxin in sera of immunized guinea pigs and mice at different intervals. Tetanus specific IgG antibodies by ELISA were found in sera of guinea pigs at ninth day after inoculation and in mice sera at seventh day after inoculation when there were no TN antibodies. Two weeks after injection of mice with aluminium phosphate adsorbed tetanus toxoid, anti-tetanus toxin IgG levels determined by ELISA were 35 to 40 times higher than the TN titers. At 4 weeks, ELISA IgG antibody levels of mice and guinea pig sera were still statistically significantly higher than TN titers but with a good correlation between ELISA and TN titers (correlation coefficient of mice sera 0.89). Mice sera at 2 weeks after two doses of tetanus toxoid (interval between doses 30 days) and 8 weeks after a single injection showed similar ELISA and TN titers (P > 0.1). Guinea pig sera at 6 weeks after a single injection showed similar TN and ELISA titers (P > 0.4). During the course of immunization in mice and guinea pigs, low avidity and low affinity IgG antibodies start appearing early which are detected by ELISA but not by TN test. Therefore ELISA results on sera before 6 weeks of immunization determined against a hyper-immune reference serum do not give a true picture of TN levels.

Animals↗

Evidence for induction of polysaccharide specific B-cell-memory in the 1st year of life: plain Haemophilus influenzae type b-PRP (Hib) boosters children primed with a tetanus-conjugate Hib-DTPa-HBV combined vaccine.

UNLABELLED: The lack of an adequate immune response to the major polysaccharide of the Haemophilus influenzae type b (Hib) capsule (polyribosyl ribitol phosphate) (PRP) in very young infants (< 18 months) can be overcome by conjugating PRP to a T-cell dependent carrier protein. We studied whether administration of a tetanus-PRP conjugate vaccine reconstituted with a diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a three dose primary course at 3, 4 and 5 months of age induced PRP-specific immunological memory, by examining the anti-PRP response to a dose of unconjugated PRP given with the DTPa-HBV booster approximately 1 year later. The unconjugated PRP elicited protective anti-PRP antibody levels (> or = 0.15 microgram/ml) in all but 3 of the 369 vaccinees, including 13 infants who failed to demonstrate a measurable immune response after the primary course. In a sub-cohort of 54 subjects all had anti-PRP levels > or = 0.5 microgram/ml within 7-14 days of the booster showing a rapid anamnestic type response. Both primary and booster responses were predominantly IgGl indicating a T-cell dependent response. The DTPa-HBV components elicited protective anti-diphtheria, anti-tetanus and anti-HBs antibody levels in > or = 98.5% of vaccinees, and immune responses to each of the acellular pertussis vaccine components in 92.3%-97.3% of subjects. CONCLUSION: The tetanus-PRP conjugate vaccine not only elicited a good primary humoral response, but also induced immunological memory so that the infants were able to mount a large and rapid immune response to subsequent exposure to plain PRP, indicating that protection against circulating wild-type Hib had been generated. Successful induction of immunological memory occurred even when there was no measurable humoral anti-PRP response to the primary course. Tetanus-PRP conjugate vaccine can be used in combination with DTPa-HBV vaccine, when administered separately or as a single injection in the same syringe, in primary immunisation schedules at 3, 4 and 5 months of age.

Age Factors↗