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PubMed2004

Tetanus immunity and physician compliance with tetanus prophylaxis practices among emergency department patients presenting with wounds.

STUDY OBJECTIVE: We determine tetanus seroprotection rates and physician compliance with tetanus prophylaxis recommendations among patients presenting with wounds. METHODS: A prospective observational study of patients aged 18 years or older who presented to 5 university-affiliated emergency departments (EDs) because of wounds was conducted between March 1999 and August 2000. Serum antitoxin levels were measured by enzyme immunoassay with seroprotection defined as more than 0.15 IU/mL. Seroprotection rates, risk factors for lack of seroprotection, and rates of physician compliance with tetanus prophylaxis recommendations by the Advisory Committee on Immunization Practices were determined. RESULTS: The seroprotection rate among 1,988 patients was 90.2% (95% confidence interval 88.8% to 91.5%). Groups with significantly lower seroprotection rates were persons aged 70 years or older, 59.5% (risk ratio [RR] 5.2); immigrants from outside North America or Western Europe, 75.3% (RR 3.7); persons with a history of inadequate immunization, 86.3% (RR 2.9); and persons without education beyond grade school, 76.5% (RR 2.5). Despite a history of adequate immunization, 18% of immigrants lacked seroprotection. Overall, 60.9% of patients required tetanus immunization, of whom 57.6% did not receive indicated immunization. Among patients with tetanus-prone wounds, appropriate prophylaxis (ie, tetanus immunoglobulin and toxoid) was provided to none of 504 patients who gave a history of inadequate primary immunization (of whom 15.1% had nonprotective antibody titers) and to 218 (79%) of 276 patients who required only a toxoid booster. CONCLUSION: Although seroprotection rates are generally high in the United States, the risk of tetanus persists in the elderly, immigrants, and persons without education beyond grade school. There is substantial underimmunization in the ED (particularly with regard to use of tetanus immunoglobulin), leaving many patients, especially those from high-risk groups, unprotected. Better awareness of tetanus prophylaxis recommendations is necessary, and future tetanus prophylaxis recommendations may be more effective if they are also based on demographic risk factors.

Adolescent↗
PubMed1998

Evaluation of the safety and pharmacokinetic profile of a new, pasteurized, human tetanus immunoglobulin administered as sham, postexposure prophylaxis of tetanus.

In a monocentric, double-blind, randomized trial, we examined the safety and pharmacokinetic profile of a new, pasteurized, human tetanus immunoglobulin (P-HTIG). As part of the purification process, P-HTIG has undergone a heat treatment step (10 h at 60 degrees C) and the removal of Merthiolate. Forty-eight adults with a history of tetanus vaccination were randomized into four groups (n = 12 per group) to receive one of two different batches of this P-HTIG simultaneously with either tetanus-diphtheria (Td) vaccine (sham, postexposure prophylaxis of tetanus) or placebo. Local reactions at the injection site were followed for the first 3 days after injection, and systemic reactions were followed during the entire study period, i.e., up to 42 days posttreatment. Blood samples for tetanus antibody titer determination (enzyme-linked immunosorbent assay method) were drawn prior to treatment on day 0 and on days 1, 2, 3, 7, 14, 21, 28, 35, and 42. A normalization of tetanus antibody titers (subtraction of the day 0 value for each subject at each time period) was performed to assess the additive effect of P-HTIG on tetanus antibody titers. The pharmacokinetic parameters were determined by both a compartmental analysis (modelization) and a noncompartmental analysis. No severe adverse reactions were reported. The rate of local reactions at the P-HTIG injection site was 27%. All local reactions were mild and resolved within 2 days. In contrast, local reactions at the vaccine injection site were seen in 79% of the subjects. The rate of systemic reactions was similar in the P-HTIG plus Td vaccine group (33%) and in the P-HTIG plus placebo group (21%), and all these reactions were mild. In the P-HTIG plus placebo group, tetanus antibody titers rose to a maximum of 0.313+/-2.49 IU/ml after 4.4 days; in the P-HTIG plus Td vaccine group, a maximum concentration of 15.2+/-2.42 IU/ml was reached 19 days postinjection. In both groups, 100% of the patients had seroprotective levels of tetanus antibodies (> or = 0.01 IU/ml) 2 days following treatment. An anamnestic response to Td vaccine appeared 7 days postimmunization. In conclusion, P-HTIG has a good safety and pharmacokinetic profile. Our results confirm that immunoglobulin should be associated with vaccine in the treatment of tetanus-prone wounds.

Adolescent↗
PubMed2006

Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP).

During spring 2005, two tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products formulated for use in adolescents (and, for one product, use in adults) were licensed in the United States (BOOSTRIX, GlaxoSmithKline Biologicals, Rixensart, Belgium [licensed May 3, 2005, for use in persons aged 10-18 years], and ADACEL, sanofi pasteur, Toronto, Ontario, Canada [licensed June 10, 2005, for use in persons aged 11-64 years]). Prelicensure studies demonstrated safety and efficacy against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adolescents. To reduce pertussis morbidity in adolescents and maintain the standard of care for tetanus and diphtheria protection, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adolescents aged 11-18 years should receive a single dose of Tdap instead of tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP)/ diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series (five doses of pediatric DTP/DTaP before the seventh birthday; if the fourth dose was administered on or after the fourth birthday, the fifth dose is not needed) and have not received Td or Tdap. The preferred age for Tdap vaccination is 11-12 years; 2) adolescents aged 11-18 years who received Td, but not Tdap, are encouraged to receive a single dose of Tdap to provide protection against pertussis if they have completed the recommended childhood DTP/DTaP vaccination series. An interval of at least 5 years between Td and Tdap is encouraged to reduce the risk for local and systemic reactions after Tdap vaccination. However, an interval less than 5 years between Td and Tdap can be used; and 3) vaccine providers should administer Tdap and tetravalent meningococcal conjugate vaccine (Menactra, sanofi pasteur, Swiftwater, Pennsylvania) to adolescents aged 11-18 years during the same visit if both vaccines are indicated and available. This statement 1) reviews tetanus, diphtheria and pertussis vaccination policy in the United States, with emphasis on adolescents; 2) describes the clinical features and epidemiology of pertussis among adolescents; 3) summarizes the immunogenicity, efficacy, and safety data of the two Tdap vaccines licensed for use among adolescents; and 4) presents recommendations for tetanus, diphtheria, and pertussis vaccination among adolescents aged 11-18 years.

Adolescent↗
PubMed1979

[The microbiological cancer test--further studies with experimental mouse tumor tetanus and wound tetanus].

A re-evaluation of the specificity of the tumour-tetanus assay of the mouse was performed by analysing the wound-tetanus assay under comparable test conditions. This was achieved by injecting 1 X 10(6) viable Ehrlich carcinoma cells admixed with 1 X 10(2) tetanus spores subcutaneously, in a 0.1 ml dose volume or, 1 X 10(2) tetanus spores suspended in 5% CaCl2 solution, respectively. By comparison, these two groups of mice developed about the same tetanus mortality rates, however, following tetanus antitoxin therapy with 3 doses of 100 IU each day on days 0, 4 and 7 after infection, clinical signs of late tetanus exclusively belonged to tumour bearing animals. This typical tetanus behaviour may be explained by a spatial-temporal association between growing tetanus rods and proliferating cells of warm-blooded animals. In this manner tumour tissue can be differed from wound granulomatous tissue by way of permanently cloning stem cells.

Animals↗
PubMed1981

Intraspinal distribution and reaction in the grey matter with tetanus toxin of intracisternally injected anti-tetanus toxoid F(ab')2 fragments.

Anti-tetanus toxoid F(ab')2 fragments were purified using immune-affinity chromatography on tetanus toxoid-Sepharose. Fragments were labeled with 125I. Labeled or non-labeled fragments were injected into the intrathecal space of rats. The labeled fragments were found in the spinal cord outside but not inside neurons. Tetanus toxin was injected into a muscle and 36 h later labeled fragments were injected intracisternally. After another 24 h the label was elevated in the spinal cord half segments giving neural supply to the injected muscle and in these half-segments the label was concentrated around some alpha-motoneurons. [125I]Tetanus toxin was injected into a muscle and at different times thereafter non-labeled fragments were injected intracisternally. The development of hindlimb rigidity but not the accumulation of [125I]tetanus toxin in alpha-motoneurons was prevented by early intracisternal injection of fragments. Injection of fragments after the appearance of hindlimb rigidity did not revert the rigidity but prevented the further development of symptoms. It is concluded that an action of tetanus toxin inside alpha-motoneurons is of no importance for the development of motor symptoms in clinical tetanus. The data suggest that in order to evoke spinal symptoms of toxicity tetanus toxin has to reach interneurons by transneuronal migration. In the very early stages of clinical tetanus the intrathecal injection of fragments may be useful.

Animals↗
PubMed2004

Alternative diphtheria, tetanus and whooping cough immunization schedule to evoke a Th2 tetanus and a Th1 pertussis immune response.

In a previous study, using BALB/c mice, we found that while diphtheria (D), tetanus (T) and whooping cough (Pw, whole-cell Bordetella pertussis) immunization induces a Th1/Th2 tetanus response and memory T cells able to proliferate in response to in vitro stimulation with B. pertussis, DTPa immunization induces a Th2 tetanus immune response and no memory T cells that recognize B. pertussis as stimulus. Considering that a pro-inflammatory cytokine production is not necessary for protection against tetanus and therefore should be avoided, an alternative DTP immunization schedule with minimal Pw exposure was assessed in order to obtain a Th2 tetanus response and a Th1 pertussis response. BALB/c mice were primed with DT vaccine at day 0, with Pw vaccine at day 14 and boosted with DTPa vaccine at days 21 and 28. A control group was inoculated with saline. Antibodies against B. pertussis surface antigens, tetanus and diphtheria toxoids were produced by mice. Spleen cells stimulated in vitro with B. pertussis produced IL-6 and IFNgamma. Only IL-5 was produced by cells in response to tetanus toxoid stimulation. These results are in line with the low IgG1/IgG2a ratio for pertussis antibodies compared with those corresponding to tetanus and diphtheria. The immunization protocol presented herein succeeded in producing tetanus and pertussis immune responses of Th2 and Th1 type, respectively. In contrast to previous results obtained with DTPw immunization, no IL-12 production was observed. Our findings provide direct evidence that an immunization protocol with an interval of 14 days between DT and Pw primings, followed by DTPa boosters, can induce appropriate immune responses against DTP vaccine antigens.

Animals↗
PubMed1998

Effectiveness of prenatal tetanus toxoid immunization against neonatal tetanus in a rural area in India.

BACKGROUND: Neonatal tetanus is the cause of 23 to 73% of neonatal deaths in developing countries and continues to be an important killer in many parts of India. METHODS: In this nonrandomized cohort study in a rural area in India, tetanus toxoid immunization status was recorded for 1688 pregnant women. Liveborn children were followed up for 30 days for the occurrence of neonatal tetanus. Nonimmunized and partially immunized women were asked their reasons for not receiving tetanus toxoid vaccine. RESULTS: Complete prenatal immunization with tetanus toxoid during pregnancy (two doses 1 month apart) was associated with an 88% reduction in the risk of neonatal tetanus among the newborn children [95% confidence interval (CI) 59 to 98%]. In multivariable analysis only complete immunization and the use of clean instruments for cutting the umbilical cord were independently associated with a reduction in risk of neonatal tetanus. Registration by the health care provider before 29 weeks of gestation, being 5 km or less from the vaccination facility, having two or more contacts with the health provider and having some school education were independently associated with complete immunization. CONCLUSIONS: Immunization of pregnant women with tetanus toxoid was the single most effective intervention against neonatal tetanus independent of other interventions.

Adult↗
PubMed2006

Combined diphtheria-tetanus-pertussis vaccine for tetanus-prone wound management in adults.

INTRODUCTION: Booster vaccination against tetanus, diphtheria and pertussis is recommended throughout life. Adults are difficult to reach and vaccination coverage in this group is often inadequate. The use of a reduced-antigen content combined diphtheria-tetanus-acellular pertussis ('adult' dTpa) vaccine for tetanus prophylaxis in emergency room wound management provides an opportunity to boost immunity against three infections simultaneously, thereby optimizing the efficiency of medical interventions with adults assessed. METHODS: A single-blind, randomized, controlled study of 320 healthy adults, the anti-tetanus antibody response within 10 days following vaccination with Boostrix (reduced-antigen diphtheria-tetanus-acellular pertussis). RESULTS: The anti-tetanus antibody response to the reduced-antigen diptheria-tetanus-acellular pertussis vaccine was equivalent to Tetavax, a licensed monovalent tetanus-toxoid vaccine. CONCLUSION: The use of diphtheria-tetanus-acellular pertussis is a safe and effective way to provide vaccination to adults against three diseases during emergency room visits for wound management.

Adult↗
PubMed2003

Tetanus in developing countries: an update on the Maternal and Neonatal Tetanus Elimination Initiative.

Tetanus is a vaccine-preventable disease that yearly causes a total of 309,000 deaths. Of particular concern is maternal and neonatal tetanus (MNT), which can be prevented through immunization of the mother in pregnancy. In 2000, neonatal tetanus alone was responsible for an estimated 200,000 deaths. While the focus is on 57 priority countries, 90% of the neonatal tetanus deaths occur in 27 countries. UNICEF is spearheading the effort to eliminate MNT by the year 2005, with the support of numerous partners. MNT elimination is defined as less than one case of neonatal tetanus per 1000 live births at district level. The main strategies consist of promotion of clean delivery practices, immunization of women with a tetanus toxoid (TT) containing vaccine, and surveillance. Maternal tetanus immunization is, in most developing countries, implemented as part of the routine immunization program. However, large areas remain underserved, due to logistical, cultural, economical or other reasons. In order to achieve the target of MNT elimination by 2005, and to offer protection to women and children otherwise deprived from regular immunization services, countries are encouraged to adopt the "high risk approach". This approach implies that, in addition to routine immunization of pregnant women, all women of child bearing age living in high risk areas are targeted for immunization with three doses of a tetanus toxoid containing vaccine (TT or Td), implemented as "supplemental immunization activities" (SIAs). Through SIAs, about 17 million women have been reached with at least two doses of TT vaccine in the past 3 years, and it is estimated that another 200 million need to be targeted in the years to come. SIAs should substantially reduce the burden of disease. Countries will also have to improve their existing immunization and clean delivery programs to ensure that the elimination of maternal and neonatal tetanus is maintained.

Adult↗
PubMed1992

Severe tetanus in immunized patients with high anti-tetanus titers.

Severe (grade III) tetanus occurred in three immunized patients who had high serum levels of anti-tetanus antibody. The disease was fatal in one patient. One patient had been hyperimmunized to produce commercial tetanus immune globulin. Two patients had received immunizations 1 year before presentation. Anti-tetanus antibody titers on admission were 25 IU/ml to 0.15 IU/ml by hemagglutination and ELISA assays; greater than 0.01 IU/ml is considered protective. Even though one patient had seemingly adequate anti-tetanus titers by in vitro measurement (0.20 IU), in vivo mouse protection bioassays showed a titer less than 0.01 IU/ml, implying that there may have been a hole in her immune repertoire to tetanus neurotoxin but not to toxoid. This is the first report of grade III tetanus with protective levels of antibody in the United States. The diagnosis of tetanus, nevertheless, should not be discarded solely on the basis of seemingly protective anti-tetanus titers.

Adult↗