Human anti-tetanus immunoglobulin(CSL Behring LLC)

The capacity of tetanus toxin to enhance motor neuron excitability has suggested its potential use as a therapeutic. Widespread active vaccination against tetanus in all developed countries is considered the major obstacle to clinical use of the toxin. We wished to determine the response to localized intramuscular injection of tetanus toxin in both passively and actively immunized animals as an initial exploration into the possible use of tetanus toxin as a clinical therapeutic. Unvaccinated mice (n=18) underwent intramuscular injection of tetanus toxin into the gastrocnemius muscle (0.2 ng, 1 ng, 5 ng). All animals in the lowest dose group developed only local tetanus of the injected limb of at least 2 weeks duration, while all animals in the higher dose groups also rapidly developed generalized tetanus and were euthanized. Another group of mice (n=20) received anti-tetanus immunoglobulin (20-40 IU) at the time of toxin injection. These animals although dramatically resistant to the toxin developed predominantly local tetanus for over one month at doses of 2.5 microg and 5.0 microg. A third group of mice (n=30) underwent active vaccination with tetanus toxoid to induce protective anti-tetanus immunity and then was challenged with high dose toxin injection (5 ng, 50 ng, 0.5 microg, 1.25 microg, 2.5 microg, or 5 microg). All animals developed local tetanus in the injected limb at a dose of at least 0.5 microg. The severity and duration of local tetanus was generally related to dose, but was more variable in the actively vaccinated group than in the naive or passively immunized animals. Response to the toxin over the first few days was predictive of both the duration and maximal severity of the motor response. Although vaccination dramatically increases resistance to tetanus toxin, by virtue of its extremely high potency, the toxin can produce prolonged localized tetanus even in vaccinated animals with relatively small amounts of protein. These results suggest the possible use of tetanus toxin to enhance local motor activity in a variety of neurologic conditions even in immunized humans. This study in uniformly vaccinated animals also illustrates the potential difficulties in determining an appropriate dose of toxin in a human population with variable degrees of immunity.

While tetanus is a rare disease in industrialized countries, this infectious disease is still responsible for up to 1,000,000 deaths per year in the developing world. In Germany, the introduction of a country-wide vaccination program (STIKO) has led to a decrease in the frequency of tetanus infection from 115 cases per year in the 1960s to fewer than 15 cases per year in the years from 1990 to 2000. In spite of all the treatment now available, tetanus infection still has a lethal outcome in up to 40% of cases. The Robert-Koch Institute recommends active or passive vaccination depending on the wound classification and the patient's current vaccination status. Since when patients have multiple trauma the emphasis while they are being treated for shock is on stabilisation and diagnosis, there is a real risk of underestimating the size and the level of contamination of existing wounds. Since it is not possible to ascertain the patient's vaccination status in most cases, we recommend simultaneous immunization of polytraumatized patients with skin lesions using Tetanol-Tetagam early in the course of the diagnostic procedures while the patients are still in the emergency room.