Effectiveness Of Tetanus Toxoid Research Articles

Summary of the NACI Update on Immunization in Pregnancy with Tetanus Toxoid, Reduced Diphtheria Toxoid and Reduced Acellular Pertussis (Tdap) Vaccine.

In Canada, pertussis is an endemic and cyclical disease, with peaks occurring at two- to five-year intervals. Although pertussis incidence varies by age group, unvaccinated or undervaccinated infants are at greatest risk of infection and associated complications. Since the last National Advisory Committee on Immunization (NACI) recommendations published in 2014, new evidence on the safety and effectiveness of tetanus toxoid, reduced diphtheria toxoid and reduced acellular pertussis (Tdap) vaccine administration in pregnancy has become available. To provide guidance on maternal immunization in pregnancy as a strategy to reduce disease incidence and severe outcomes (defined as hospitalization or death) from pertussis infection in infants less than 12 months of age. The NACI reviewed evidence on the burden of disease in Canada, vaccine safety and immunogenicity and vaccine effectiveness in jurisdictions that have implemented maternal immunization programs. A total of 59 articles were identified, retrieved and included in the literature review to inform this statement. In the majority of reviewed studies, post immunization increases in antibody levels resulted in more than 90% of women achieving anti-PT levels greater than or equal to 10 IU/ml one month following immunization. In infants, maternal immunization was found to result in increased pertussis antibody concentrations. In the majority of studies, following the receipt of the fourth diphtheria, tetanus and pertussis (DTaP) dose after 15 months of age, no statistically significant differences in antibody levels and avidity were observed between infants whose mothers received Tdap in pregnancy and those whose mothers did not receive Tdap in pregnancy. No major maternal or infant safety issues, including pregnancy outcomes, were reported in the reviewed literature. Effectiveness of maternal Tdap immunization in pregnancy was estimated to be over 90% against pertussis in infants younger than two months of age, with no deaths observed among infants whose mothers received Tdap prior to 36 weeks of pregnancy. Maternal immunization with Tdap in pregnancy also resulted in a reduction in infant disease severity and hospitalization. Vaccine effectiveness was also reported to persist after the receipt of the first three DTaP doses, with immunization in pregnancy resulting in additional protection of up to 70% in children whose mothers received Tdap in pregnancy. There is now strong evidence to support the NACI recommendation that immunization with Tdap vaccine should be offered in every pregnancy. This is ideally administered between 27 and 32 weeks of gestation but evidence also supports providing maternal Tdap over a wider range of gestational ages, from 13 weeks up to the time of delivery, in view of programmatic and unique patient considerations.

Vaccines for women for preventing neonatal tetanus.

Tetanus is an acute, often fatal, disease caused by an exotoxin produced by Clostridium tetani. It occurs in newborn infants born to mothers who do not have sufficient circulating antibodies to protect the infant passively, by transplacental transfer. Prevention may be possible by the vaccination of pregnant or non-pregnant women, or both, with tetanus toxoid, and the provision of clean delivery services. Tetanus toxoid consists of a formaldehyde-treated toxin that stimulates the production of antitoxin. To assess the effectiveness of tetanus toxoid, administered to women of reproductive age or pregnant women, to prevent cases of, and deaths from, neonatal tetanus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015), CENTRAL (The Cochrane Library 2015, Issue 1), PubMed (1966 to 28 January 2015), EMBASE (1974 to 28 January 2015) and reference lists of retrieved studies. Randomised or quasi-randomised trials evaluating the effects of tetanus toxoid in pregnant women or women of reproductive age on numbers of neonatal tetanus cases and deaths. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two effectiveness trials (9823 infants) and one safety trial (48 mothers) were included. The main outcomes were measured on infants born to a subset of those randomised women who became pregnant during the course of the studies. For our primary outcomes, there was no high-quality evidence according to GRADE assessments.One study (1182 infants) assessed the effectiveness of tetanus toxoid in comparison with influenza vaccine in preventing neonatal tetanus deaths. A single dose did not provide significant protection against neonatal tetanus deaths, (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.26 to 1.24; 494 infants; GRADE: low-quality evidence). However, a two- or three-dose course did provide protection against neonatal deaths, (RR 0.02, 95% CI 0.00 to 0.30; 688 infants; GRADE: moderate-quality evidence). Administration of a two- or three-dose course resulted in significant protection when all causes of death are considered as an outcome (RR 0.31, 95% CI 0.17 to 0.55; 688 infants; GRADE: moderate-quality evidence). No effect was detected on causes of death other than tetanus. Cases of neonatal tetanus after at least one dose of tetanus toxoid were reduced in the tetanus toxoid group, (RR 0.20, 95% CI 0.10 to 0.40; 1182 infants; GRADE: moderate-quality evidence).Another study, involving 8641 children, assessed the effectiveness of tetanus-diphtheria toxoid in comparison with cholera toxoid in preventing neonatal mortality after one or two doses. Neonatal mortality was reduced in the tetanus-diphtheria toxoid group (RR 0.68, 95% CI 0.56 to 0.82). In preventing deaths at four to 14 days, neonatal mortality was reduced again in the tetanus-diphtheria toxoid group (RR 0.38, 95% CI 0.27 to 0.55). The quality of evidence as assessed using GRADE was found to be low.The third small trial assessed that pain at injection site was reported more frequently among pregnant women who received tetanus diphtheria acellular pertussis than placebo (RR 5.68, 95% CI 1.54 to 20.94; GRADE: moderate-quality evidence). Available evidence supports the implementation of immunisation practices on women of reproductive age or pregnant women in communities with similar, or higher, levels of risk of neonatal tetanus, to the two study sites.

Determinants of Utilization of Sufficient Tetanus Toxoid Immunization During Pregnancy: Evidence from the Kenya Demographic and Health Survey, 2008–2009

Although the effectiveness of tetanus toxoid (TT) immunization during pregnancy in preventing maternal and neonatal tetanus is well established, in many developing countries, TT immunization programs are underutilized. The objective of this study was to examine factors associated with sufficient TT immunization among postpartum women in Kenya. Population based secondary data analysis was conducted using de-identified data from the 2008-2009 Kenyan Demographic and Health Survey (KDHS) for 1,370 female participants who had a live birth during or within 12 months of the cross-sectional survey. Chi-square test and independent sample t test were conducted to assess bivariate associations and a multivariable logistic regression analysis was conducted to examine associations before and after adjustment for demographic, socioeconomic, cultural, and access to care factors. The main factors contributing to having been sufficiently immunized against tetanus were lower birth order, higher household wealth index, women's employment, making joint health-related decisions with a partner, and higher number of antenatal care visits. Implications for health care providers and other professionals involved in development of strategies and interventions aimed at improving immunization rates are discussed.

The effect of meningococcal serogroup A polysaccharide-protein conjugate vaccine prepared with TT and rCTB on mucosal immune responses

Objective To analyze the feasibility of the recombinant cholera toxin B subunit (rCTB) as a carrier protein candidate for the preparing of polysaccharide-protein conjugate, and to discuss the immune effects of tetanus toxoid (TT) as the carrier protein in mucosal delivery vaccine. Methods The refolded pentrumer protein, rCTB was obtained by genetic engineering methods. Then conjugated the refold-ed protein with group A meningococcal polysaccharide (GAMP) using the chemical method(ADH) ,the pol-ysaccharide-protein conjugates(GAMP-rCTB) were prepared. BALB/c mice were immunized either intraper-itoneally ( i. p. ) or intranasally ( i. n. ) with GAMP-rCTB. Moreover, GAMP-TT vaccine that TT as carrier proteins was i.n. immunized to the mice. The evaluation of immunology is performed. Results The conju-gates of polysaccharide-potein with the rCTB and TT as protein carrier both are able to elicit high level of GAMP specific IgG antibody in serum after i.n. immunization, and the conjugates can also elicit specific IgA antibody in lung lavage and intestinal mucosa. Conclusion rCTB and TT can both as the protein carri-er for polysaccharide-protein conjugate as mucosal vaccine. The route of intranasal may be more ways for im-mune function than i.p. immunization when rCTB is used as the carrier of the polysaccharide-protein conju-gates. Key words: Polysaccharide-protein conjugate vaccine; Protein carrier; Tetanus toxoid(TT) ; Re-combinant cholera toxin B subunit (rCTB)

Inhibition of Lymphocyte Proliferation Induced In Vitro by Microbial Antigens in HIV‐Infected Subjects

In the course of a study of lymphocyte responses to microbial antigens in HIV-infected patients, we detected a previously unrecognized phenomenon of inhibition of lymphocyte baseline proliferation, induced by the presence of tetanus toxoid and Escherichia coli in the cultures. The effects of tetanus toxoid and Escherichia coli on lymphocyte proliferation in vitro were assessed by comparing the 3H-thymidine uptake by lymphocytes cultured without stimulant with the uptake of lymphocytes cultured in the presence of the antigens. Twenty-six patients with HIV infection (20 asymptomatic/persistent generalized lymphadenopathy, 2 AIDS-related complex, 4 AIDS) were investigated and the controls were 33 healthy individuals without evidence of HIV infection. Eight out of 22 asymptomatic/PGL and ARC patients progressed to full-blown AIDS in the mean follow-up of 26 months. The inhibition of proliferation was considered to be significant when the uptake of 3H-thymidine was reduced by 20% in the presence of the antigens. Using these criteria, 50% of the patients studied with tetanus toxoid and 36% of those studied with E. coli had evidence of the inhibitory phenomenon. Seven of the eight patients who developed AIDS during the observation period had the inhibitory phenomenon. In the group of patients without the inhibitory signs only one evolved to AIDS during the follow-up. The possibility of this phenomenon being related to an induction of suppressor cell activity by the antigens is discussed.

Does training TBAs prevent neonatal tetanus?

The evidence for the effectiveness of training traditional birth attendants (TBAs) as a way to prevent neonatal tetanus in areas of the developing world is reviewed. The ultimate test of the effectiveness of TBA training in relation to neonatal tetanus is whether or not it makes an impact on neonatal tetanus incidence and mortality rates. Evidence on this comes from 4 major sources: studies of programs based on TBA training only and those including both tetanus toxoid immunization and TBA training studies of cases based on hospital admissions and controlled trials of TBA training. There have been few studies of TBA training in the absence of tetanus toxoid immunization since the effectiveness of tetanus toxoid was demonstrated in the 1960s. Programs have tended to include both immunization as well as TBA training. There have been several studies of neonatal tetanus incidence in programs in which TBAs have been trained as part of a more comprehensive health program which also included toxoid immunization. The findings of 3 such studies -- a project in Serabu Hospital in Sierra Leone the Bohol Project in the Philippines and a general review of selected provinces in the Philippines -- are summarized. The results of these studies are impressive yet it is not possible to assess what proportion of the observed declines in neonatal tetanus incidence was due to improved prenatal care and what proportion was due to increased tetanus toxoid immunization rates in pregnant women since all programs encouraged both. In at least 2 of the studies some of the cases were delivered by trained TBAs and others by untrained TBAs. These studies tell nothing about whether training TBAs decreases the incidence of neonatal tetanus but only that it did not totally eliminate neonatal tetanus among the children they delivered. A review of the literature revealed 4 controlled trials of TBA training and neonatal tetanus; these are summarized. As this review demonstrates evidence that TBA training on its own leads to a reduction in neonatal tetanus incidence is inconclusive. None of the relatively few studies that have been published thus far stand up to a detailed methodological scrutiny though the vast majority are encouraging rather than discouraging. Yet there is conclusive evidence that tetanus toxoid immunization either of all pregnant or of all women in the childbearing age group can eliminate neonatal tetanus. TBA training and tetanus toxoid immunization are not mutually exclusive and all TBAs should be taught the importance of tetanus toxoid immunization and be trained to encourage women to receive it.