In Korea, Td vaccine has been available after 2004 (6
). Before that year, tetanus prophylaxis should be done by only TIG at the ED or at a general hospital. Nevertheless, there have been approximately 10 tetanus patients have been reported each year, even after complete vaccination during childhood and tetanus prophylaxis with TIG at ED after injury. Though Td has recently been available for immunization and prophylaxis, Td and Td vaccination in adults are not covered by the national health insurance in Korea. Td and Td vaccination are expensive, so most adults' vaccination have been done with Td only at the ED after injury and the adults who had not received previous tetanus vaccination with Td after childhood generally were not vaccinated according to the adult tetanus vaccination schedule. Male adults entering the military service after 1975 must be vaccinated with tetanus toxoid. Tetanus vaccinations at the time of military service and at the ED after injury have been almost the only chance to elevate the tetanus antibody titer in adults. Therefore tetanus prophylaxis at the ED after injury would be very important immunization opportunity for elevating an individual tetanus antibody titer. Most emergency physicians in Korea have been directed to perform tetanus prophylaxis with Td and TIG for injured adult patients because of their low tetanus antibody titer and the low rate of previous tetanus active immunization. In our study, simultaneous injection of Td and TIG did not diminish on tetanus immunity.
The tetanus antibody level after simultaneous administration of Td and TIG was lower than that after a Td single injection in a previous study (7
), which provoke some controversies. First, in group 2 (Td + TIG) the basal GMTs were lower than that of group 1 (Td), and statistical significant differences were not shown in the basal GMTs between the groups, but adjustment of the basal GMTs might have been needed. Second, the enrolled subjects were young with a mean age of 26 yr, so a limitation of the adult age distribution existed. Third, follow-up of this study was done for only 4 months and additional follow-up was not done. Significant differences of the GMTs between the groups existed at 4 weeks, but these were not seen at 4 months after immunization. In our study, the GMTs at 4 weeks were significantly different between the groups, but there were no significant differences at 6 and 12 months follow-up. Also, time and age were not meaningful factors for the change of the tetanus antibody level after tetanus prophylaxis in our study by using the mixed model after adjustment of other factors.
There were significant differences of the GMTs in the male subjects between the groups after adjustment of the baselines GMTs and age, but these differences did not exist in the female subjects. However, there was not an exact explanation about these differences between male and female subjects. There were also significant differences of the GMTs in the patients over 60 yr between the groups after adjustment, but not for the patients below 60 yr. In Korea, complete child vaccination had started in 1956 and vaccination at the beginning of military service had started in 1975; therefore, now most the subjects who were over 60 yr might not have been immunized at childhood and during military service when they were young adults (8
). Further study and investigation are needed to determine and explain the significantly high GMTs in the males and the people over sixty in our country.
There have been some studies about the simultaneous administration of hepatitis immunoglobulin and vaccine (9
). Those studies showed that the hepatitis antibody titers were not significantly different when comparing between the injection of vaccine alone group and the simultaneously injecting vaccine plus immunoglobulin group. The antibody titers in the recipients of vaccine alone were slightly but significantly higher than those of the subjects who received both hepatitis immunoglobulin and vaccine during the several months. In the late months, however, these differences were no longer statistically significant. These hepatitis researches were very similar to our results that tetanus immunoglobulin did not interfere with the development of an active antibody response to the vaccine during a relatively long time. When live attenuated vaccine is injected to humans according to the vaccination schedule, the simultaneous injection of immunoglobulins is usually not recommended because the simultaneous administration of immunoglobulin with vaccines could reduce the immunogenicity for protective antibody production. Yet for inactivated vaccines, the simultaneous administration of immunoglobulins and vaccines is considered feasible (11
). The tetanus vaccine is an inactivated vaccine, so co-administration with immunoglobulin is possible.
According to the general guideline of tetanus vaccination to inoculators who had not been immunized as adults, a three shot booster schedule is recommended at 0, 1 and 6 months or at 0, 1 and 12 months. Because no statistical significant difference existed between a single injection of Td and the simultaneous injection of Td plus TIG in this study, if the first vaccination was done by co-administration of vaccine and immunoglobulin at the ED for the first time during adulthood, then the next vaccination may be followed according to the recommended schedule.
In summary, the level of tetanus antibody after tetanus vaccination is not influenced by TIG as observed at 6 and 12 months, and in adults below 50 yr, but are significantly different between the two groups at 4 weeks and for the patients over 60 yr.