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PubMed1993

Should adult tetanus immunization be given as a single vaccination at age 65? A cost-effectiveness analysis.

OBJECTIVE: To compare three vaccination strategies for the prevention of adult tetanus. Each strategy includes childhood primary immunization and wound prophylaxis, and one of the following: 1) the currently recommended booster every ten years; 2) a single booster at 65 years of age; or 3) no intervention after age 6 except for wound prophylaxis. METHODS: Cost-effectiveness analysis was used to compare the three different strategies. A Markov model, cycled annually from age 5 through age 85, was applied to each strategy to predict the incidence and costs of tetanus for the U.S. adult population. RESULTS: The three strategies have very similar effects on life expectancy but different costs. Expressed incremental to no intervention after childhood primary immunization, the decennial booster strategy is least cost-effective, with a discounted incremental cost-effectiveness ratio of $143,138 per year of life saved compared with $4,527 for the single-booster strategy. Sensitivity analysis demonstrates that the decennial strategy is more effective but more costly over a wide range of model assumptions. CONCLUSIONS: The current policy of recommending tetanus booster vaccinations every ten years is effective but much more costly than a more easily implemented policy that also provides considerable protection against tetanus. The authors recommend forsaking decennial boosters in favor of a policy of including a single booster at age 65 along with other recommended health maintenance maneuvers reserved for that age.

Adolescent↗
PubMed1990

Use of chromatography for the preparation of homologous tetanus antitoxin.

To obtain immunoglobulin of selected action with a higher titre, techniques for isolating antibodies from a donor's normal immunoglobulin by means of affinity chromatography were used. To obtain an affinity sorbent, tetanus toxoid was used as a ligand. Using an immunosorbent based on the purified ligand, tetanus antibodies were prepared with a specific activity of 65 IU/mg. According to gel-permeation chromatography, the tetanus antibodies obtained were represented mainly by IgG monomer (greater than 90%). The anticomplementary activity of the preparations obtained, being at least 11 mg of protein per 2CH50, does not rule out the possibility of intravenous administration of tetanus antibodies.

Chromatography, Affinity↗
PubMed1985

Interaction of solid-phase gangliosides with tetanus toxin and toxoid.

Tetanus toxin has been fractionated on a column of silica beads coated with a ganglioside mixture. Toxicity and affinity of the fractions for brain membranes increased with their affinity for the column. The toxicity recovered with the nonabsorbed fraction was less than 5% with respect to the unfractionated toxin or its firmly bound moiety. Tetanus toxoid yielded less toxic or nontoxic fractions with different affinities for the column. Accordingly, binding of tetanus toxoid to brain membranes was partially preserved under mild toxoiding with formaldehyde. It is concluded that binding to gangliosides is a necessary, but not a sufficient, precondition for the pharmacological activity of tetanus toxin and its derivatives.

Animals↗
PubMed1988

The toxin binding inhibition test as a reliable in vitro alternative to the toxin neutralization test in mice for the estimation of tetanus antitoxin in human sera.

A method for the screening of human sera for tetanus antibodies has been developed and evaluated. The toxin binding inhibition test (ToBI-test) is based on inhibition of the binding of tetanus toxin to an antitoxin-coated immunoassay microtitre plate by tetanus antibodies. Serum samples from 191 healthy adults with different vaccination histories have been titrated for tetanus antibodies by the toxin neutralization (TN) test in mice, by toxoid-ELISA and by the ToBI-test. In every respect, the ToBI-test proved to be the best in vitro alternative to the TN-test in mice. Comparisons showed a higher degree of correlation between the ToBI-test and the TN-test than between the toxoid-ELISA and the TN-test. Furthermore, no overestimation of antibody content was seen in titrating low titre sera by the ToBI-test. In contrast, several false positive results were seen when using the toxoid-ELISA. It is concluded that the ToBI-test is a reliable and precise alternative to the TN-test and can be performed under simple laboratory conditions in a short time.

Animals↗
PubMedDate not supplied

Tetanus toxin as a neurobiological tool to study mechanisms of neuronal cell death in the mammalian brain.

Tetanus toxin is a potent clostridial neurotoxin responsible for causing spastic paralysis in humans, often accompanied by seizures and death. The tetanic syndrome is believed to originate from a disinhibitory action of the toxin in the CNS. To produce its effects, tetanus toxin undergoes retrograde, intra-axonal transport to the CNS, where it blocks preferentially the release of gamma-aminobutyric acid and glycine, two inhibitory neurotransmitters. These effects stem from the cleavage of synaptobrevin, a constitutive small-vesicle protein, by tetanus toxin, whose zinc-dependent metalloprotease characteristics recently have been recognized. Blockade of inhibitory transmission produces a predominance of excitatory amino acid neurotransmission, which is responsible for the neurodegenerative effect caused by tetanus toxin after intrahippocampal injection in rats. In fact, hippocampal damage can effectively be prevented by reduction of glutamate-mediated excitatory transmission, thus suggesting that unopposed excitation may be the underlying mechanism for neuronal cell death.

Animals↗
PubMed1991

Maternal tetanus immunization in Aceh Province, Sumatra: the cost-effectiveness of alternative strategies.

This paper compares the cost per completed maternal tetanus immunization and an estimate of the cost per death averted in the routine EPI program with similar results from an experimental mass campaign in Aceh Province, Indonesia. The cost-effectiveness of the mass campaign in achieving complete immunization is similar to the routine program. However, the mass campaign is probably less cost-effective in averting neonatal tetanus deaths, due to its broader targetting. Factors affecting efficiency, coverage, and financing of tetanus immunization programs are assessed. While expansion of the routine EPI program is the preferred goal, mass campaigns are judged to be a reasonable part of the multi-year strategy for tetanus control in the province. Recent experiments with an accelerated routine program may provide further alternatives.

Adolescent↗
PubMed1995

Cross cultural communication of tetanus vaccinations in Bolivia.

Although neonatal tetanus (NNT) is common in developing countries, many people are unaware of its causes and prevention. A study analyzed cultural beliefs and practices to understand how people in three cultural areas in Bolivia (Aymara, Quechua and Tupi-Guarani) think about NNT and tetanus toxoid (TT) immunizations. In all three cultural areas NNT is perceived within a magical and biological framework that involves alternative healing systems and healers. Tetanus immunization programs could be more successful if tetanus were a clearly marked target for the Aymara, Quechua and Tupi-Guarani people, and vaccinators were sensitive to their cultural perceptions. Health workers need to communicate cross-culturally the relationship of TT vaccinations to how members of these ethnic groups perceive NNT.

Attitude to Health↗
PubMed2004

Case report of tetanus in an immunized, healthy adult and no point of entry.

We report the case of a 58-year-old man born in the United States with a history of complete childhood immunizations who presented to the Emergency Department with trismus. Past medical history was significant only for Elephantiasis. After an exhaustive workup the patient was found to have Tetanus, with no identifiable portal of entry. The patient was successfully treated for Tetanus with complete recovery. Tetanus is caused by the organism Clostridium Tetani, which usually requires an open lesion to cause infection. Our patient was unique in that he was previously immunized with no obvious lesion. Tetanus should be suspected and treated empirically in any patient presenting with typical signs and symptoms even without an apparent entry site.

Anti-Infective Agents↗
PubMed2004

Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in adults.

Two clinical studies were undertaken to evaluate the immunogenicity of an adult-type dTpa booster vaccine (Boostrix by GlaxoSmithKline Biologicals). Blood samples taken prior to vaccination showed that 24.4 and 13.0% of subjects were seronegative for diphtheria and tetanus antibodies, respectively. Moreover, about one-third of the vaccinees had no detectable levels of antibodies to pertussis toxoid (PT) or pertactin (PRN). One month post-vaccination, more than 93% of all individuals, regardless of age or type of vaccine received, had seroprotective antibody levels for diphtheria and tetanus (> or = 0.1IU/ml). In those individuals vaccinated with the adult-type dTpa vaccine (Boostrix), more than 98% were found to be seropositive for antibodies to all three pertussis antigens (PT, filamentous haemogluttin (FHA), and PRN). These data suggest that immunity to diphtheria, tetanus and pertussis (DTP) in adults wanes and that booster vaccination with an adult-type combined dTpa vaccine would boost the serological response to diphtheria antitoxin, tetanus antitoxin and antibodies to Bordetella pertussis PT, FHA and PRN.

Adolescent↗
PubMed2005

Insufficient protection for healthy elderly adults by tetanus and TBE vaccines.

Little information is available on post-vaccination antibody concentrations and the duration of protection in persons of more than 20 years of age. We, therefore, measured antibodies specific for tetanus (TT) or tick-borne encephalitis (TBE) virus in 734 adults (age 18-93 years, 382 females and 352 males) and evaluated these data in connection with the time point of the last vaccination against tetanus or TBE and age. This analysis revealed that the time of the last vaccination as well as age had highly significant effects on tetanus and TBE titers (p < 0.001). Our results show a strong decline in post-vaccination antibody concentrations with age, which sets in at the age of 40 in the case of tetanus, and is observed right throughout adult life in the case of TBE. Persons over 60 years of age frequently do not have protective antibody concentrations. We conclude that immunological responsiveness to vaccination decreases throughout adult life, and that conventional vaccination strategies designed for children and young adults cannot be uncritically applied in the elderly.

Adolescent↗
PubMed1975

Tetanus in Haiti.

In 1958-72, 985 cases of tetanus (excluding tetanus of the newborn) were admitted to a hospital in Haiti. Mortality was 22%, and in later years (1966-72) mortality fell. During this period the dosage of tetanus antitoxin was lowered to 10,000 units and, for sedation, diazepam has satisfactorily replaced multiple-drug regimens used in earlier years. However, good nursing, including close attention to breathing, is probably the most important item in treatment. As a result of a programme of maternal immunisation, admissions for neonatal tetanus have fallen, and mortality for this condition has been reduced to 26%.

Aged↗
PubMedDate not supplied

Rational approaches to reduce adverse reactions in man to vaccines containing tetanus and diphtheria toxoids.

Adverse reactions to routine vaccines are obstacles to the mass vaccination campaigns. Though the absolute safety of any injectable vaccine cannot be guaranteed, the adverse side effects to vaccines can be minimized by practicing existing scientific knowledge. Adverse side effects to tetanus and diphtheria toxoids have been known for many years and there have been ways to minimize these reactions. These procedures did not get wide acceptance, because the current partially purified tetanus and diphtheria vaccines meet the regulatory requirements and the manufacturers are reluctant to change the established procedures of production due to the amount of work involved in the regulatory issues under the current Good Manufacturing Practices (GMP). Due to the recent epidemic of diphtheria in the independent states of the former Soviet Union, and its potential for spread to other European Countries, vaccination campaigns with tetanus and diphtheria vaccines received a new boost with several international agencies. In this report, we review the causes for adverse reactions to tetanus and diphtheria vaccines and offer practical suggestions for minimizing these reactions. The major issues in minimizing adverse reactions to these vaccines include: (1) purifying the toxins before detoxification as the reactogenic accessory antigens get covalently bound to the toxins during detoxification; (2) either using well-tolerated adjuvants which do not elicit the production of antigenic specific IgE antibodies responsible for adverse reactions or by using non-adjuvanted highly immunogenic polymerized antigens; (3) checking the status of immunity by recently developed rapid serological methods or by the Schick skin-test for diphtheria to avoid allergic or Arthus-type reactions. These approaches are applicable to industrial scales and would result in a pure, less reactogenic and better characterized toxoids antigens which would be more suitable for combined vaccines comprising highly purified acellular pertussis components, polysaccharide-protein conjugates and other antigens.

Adjuvants, Immunologic↗
PubMed1999

Seroprevalence and determinants of diphtheria, tetanus and poliomyelitis antibodies among adults in Berlin, Germany.

The immunity levels against diphtheria, tetanus and poliomyelitis were investigated among blood donors (n = 2079) in Berlin. Of all participants, only 60% had full, long-term protection against diphtheria, 72% against tetanus, 87% against poliomyelitis type 1, 77% against poliomyelitis type 2 and 73% against type 3. There was a striking decrease of tetanus and diphtheria immunity levels by age. Immunity levels against tetanus were higher among males, whereas females were better protected against poliomyelitis. After adjusting for confounding effects in logistic regression diphtheria immunity in those aged <40 years was significantly higher in participants from East-Berlin, whereas the immunity levels against poliomyelitis were higher in West-Berlin. These differences reflect the different vaccination policies in East-Germany and West-Germany before 1989. There is a need to improve the immunity levels of the adult population in Berlin.

Adolescent↗
PubMed1999

Immunogenicity of IRIV- versus alum-adjuvanted diphtheria and tetanus toxoid vaccines in influenza primed mice.

The immunogenicity and protectivity of two different toxoid vaccines were compared in mice. In one formulation, toxoids (diphtheria or tetanus) were adsorbed to alumoxid, whereas in the other formulation the toxoids were crosslinked to immunopotentiating reconstituted influenza virosomes (IRIVs). A preimmunization with influenza antigens is necessary for a good anti-toxoid antibody response when the IRIV formulation was administered. After two immunizations with the IRIV- or alum-based vaccines, the IRIV-based formulation induced a higher humoral immune response than toxoids adsorbed to alum. Using an in vitro test, diphtheria toxin neutralizing antibodies were tested. Di-IRIV induced a significantly (p = 0.002) higher titer of diphtheria toxin neutralizing antibodies than Di-alum. Tetanus challenge experiments showed, that the IRIV-based tetanus vaccine induced a threefold higher titer of protective antibodies than the tetanus toxoid adsorbed to alum. Therefore, the IRIV-based formulations appeared to be superior to the alum-based vaccines in terms of immunogenicity and protectivity.

Adjuvants, Immunologic↗
PubMed2000

A randomised controlled trial with a diphtheria-tetanus-acellular pertussis (dTpa) vaccine in adults.

The aim of this assessor-blinded trial was to compare the immunogenicity and reactogenicity of a candidate diphtheria, tetanus toxoids and acellular pertussis vaccine with reduced antigen content for diphtheria and pertussis (dTpa) with a licensed reduced adult-type diphtheria-tetanus vaccine Td (reduced diphtheria content) and with an experimental candidate monovalent acellular pertussis vaccine with reduced antigen content (pa). The dTpa and pa vaccines had identical pertussis antigen content. A total of 299 healthy adults (> or =18 years, mean age: 30.1 years+/-10.7) were randomised into 3 groups to receive a single dose of one of the study vaccines. In all groups, clinically significant reactions (severe) were infrequent (0-6%) and no serious adverse events were reported during the study. The incidence of local and systemic reactions following the administration of dTpa was comparable to the Td vaccine group. Of the total study group, prior to vaccination 52. 3 and 93.2% of the subjects had anti-diphtheria and anti-tetanus antibody levels > or = 0.1 IU/ml, respectively; and 73.1, 98.2 and 74.5% of the subjects were seropositive for pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) antibodies, respectively. One month after vaccination, a similar percentage of subjects in the dTpa and Td groups had anti-diphtheria (88.4% vs 90. 1%) and anti-tetanus (100% vs 98.9%) antibody levels > or =0.1 IU/ml. Similar anti-FHA (100%) and anti-PRN (98.9%) vaccine response rates were seen in the dTpa and pa groups, while the anti-PT vaccine response rates were 96.8 and 100.0%, respectively. The dTpa vaccine is as well tolerated and immunogenic as the licensed Td vaccine, and additionally, can also boost antibodies against pertussis.

Adhesins, Bacterial↗
PubMed1992

Simplified activity evaluation of several tetanus vaccines.

The activity of several Tetanus Toxoids, Adsorbed, (commercial vaccines and references) were tested in mice in comparison with a standard, by a simple method, easier than the official challenge test (WHO and European Pharmacopoeia): the Tetanus Antitoxin level was titrated by agglutination of sensitized turkey red blood cells after immunization by the toxoids. Immuno-stimulation by the Pertussis component in associated vaccines was studied and the results with the conventional and the acellular Pertussis preparations were prepared. The method was also found to be suitable for Tetanus Toxoids, Non-Adsorbed, when a booster effect was used, except for the adjuvant-free polymerized antigen (POLAN) which did not require a booster, since it gave almost as good results as conventional adsorbed tetanus vaccines.

Animals↗
PubMed1992

Use of the nirB promoter to direct the stable expression of heterologous antigens in Salmonella oral vaccine strains: development of a single-dose oral tetanus vaccine.

Plasmid pTETnir15, which directs the expression of the non-toxic immunogenic fragment C of tetanus toxin from the anaerobically inducible nirB promoter, was introduced into the Salmonella typhimurium aroA aroD live oral vaccine strain BRD509. The resulting strain, designated BRD847, was used to vaccinate orally BALB/c mice and was tested for plasmid stability and its ability to protect against a lethal tetanus toxin challenge. pTETnir15 was stably inherited by bacteria growing or persisting in the tissues of immunized mice whereas another BRD509 derivative, designated BRD753, harboring plasmid pTET85 which directs fragment C expression from the tac promoter, was highly unstable. Mice immunized with a single oral dose of BRD847 developed high levels of circulating anti-fragment C antibodies and were solidly protected against tetanus toxin challenge. Mice immunized with a single oral dose of BRD753 developed no detectable anti-fragment C antibodies. After boosting, antibodies were detected, but the mice were only partially protected against tetanus toxin challenge. Thus the use of an in vivo inducible promoter such as nirB may be a generally applicable approach to obtaining the stable in vivo expression of heterologous antigens in Salmonella vaccine strains.

Anaerobiosis↗
PubMed1997

A randomized comparison between early and late vaccination with tetanus toxoid vaccine after allogeneic BMT.

Forty-five adult HLA-matched sibling BMT recipients were randomized to receive tetanus toxoid (TT) vaccine at 6, 8 and 14 months (early group, n = 23) or at 18, 20 and 26 months after BMT (late group, n = 22). At 6 months after BMT, prior to the first vaccination, 90% of the early group patients had a protective tetanus antibody concentration of > or = 0.1 HU/ml (passive haemagglutination test) but only 70% of the late group patients did so at 18 months after BMT. The antibody responses 1 month after each of the three TT vaccine doses were similar in the two vaccination groups, except that after the first dose, four-fold responses occurred more frequently in the late group. All vaccinated patients achieved the protective antibody concentration of > or = 0.1 HU/ml. In the late group the recipient antibody responses after the first and second vaccine doses correlated with the donor anti-TT level. A tetanus vaccination schedule consisting of three vaccine doses is equally immunogenic when started at 6 or 18 months after BMT. Donor immunity against tetanus may influence recipient responses to TT vaccination.

Adolescent↗