Administration of tetanus toxoid [TT] to pregnant women versus tetanus and reduced diphtheria [Td]: a randomized controlled

ABSTRACT

We conducted a clinical trial to compare the immunogenicity, reactogenicity and efficacy of Tetanus Toxoid [TT] and the combined Tetanus and reduced Diphtheria [Td] in pregnant women residing four rural communities in Egypt. The study has been designed as a randomized controlled trial. Pregnant women in each of the four villages received either TT or Td randomly. Both TT and Td vaccines are manufactured by the Egyptian Company for Biological Products and Vaccines [VACSERA] in Egypt. A total of 131 pregnant women were enrolled at the time of their antenatal care visit [at the beginning of their fifth gestational month] to one of four health units in Abu Homos district, Beheira Governorate, Egypt. Previously un-immunized women received at random 2 doses of TT or Td eight weeks apart during their pregnancy. Active outpatient follow-up for adverse events was done on the third day after each dose. Local [pain, redness and swelling] or general [fever, malaise and headache or body aches] reactions during the 3-day post-dosing interval served as the primary safety end point. Blood was collected 3 times from each subject to detect antibody level against tetanus and diphtheria by ELISA. The first sample was collected immediately before the first dose, the second before the 2[nd] dose and the third sample one week after delivery. Active surveillance home visits to all study participants were conducted twice. The first home visit was during the first week after delivery and the second one month after labor to report the health status of the mother and the baby. A total of 122 pregnant women received 2 correct doses had inter-dose intervals within the allowable range and provided 3 samples of blood, were included in per protocol analysis [62 in the TT group and 60 in the Td group]. There was no statistically significant inter group difference in the percentage of subject reporting the primary safety endpoint [fever, malaise, body ache, headache] or local reactions at the site of injection as redness and swelling, during the 3-day after each dose. There was a statistically significant greater reporting of pain at injection site in the Td group after dose I and II compared to the TT group. Home visits revealed normal mothers and babies on clinical examination in both groups. However, more babies in the TT group suffered from physiological jaundice. All women in the two groups acquired protective immunity for tetanus, determined as possession of neutralizing antibodies at titre>0.10 IU/ml after completing vaccination. However, the geometric mean titres of tetanus post dose I and II were significantly higher in vaccinees in the TT group [P<0.001]. For diphtheria, post vaccination seroprotection [titre>0.10 lU/ml] was significantly higher in the group received Id than the TT group. Geometric mean Titres of diphtheria post dose II were significantly higher in vaccinees in the Td compared to the other group [P<0.0001]. These finding demonstrared that the use o Td vaccine improves immunogenicity for both tetanus and diphtheria over the use of 'IT vaccine alone and may be recommended to replace TT in immunization of pregnant women.