Vaccines for women to prevent neonatal tetanus

Antitetanus vaccination in multiple doses (2–3) is up to 98% effective in preventing neonatal tetanus and neonatal tetanus deaths in under-resourced settings. Single doses of the tetanus vaccine are not enough to prevent neonatal tetanus deaths. In addition to administration of antitetanus vaccines, efforts should be made to ensure that women receive obstetric care to ensure clean deliveries.

RHL Commentary by Ogunlesi TA

1. INTRODUCTION

Neonatal tetanus rarely occurs nowadays in the developed countries and technologically advanced parts of the developing world as a result of the successful elimination of the disease from such settings. This was achieved with effective vaccination and clean deliveries (1).

Neonatal tetanus has been described as a manifestation of poverty and inequity in the distribution and utilization of health-care services (1). Epidemiological evidence strongly suggests that risk factors for neonatal tetanus include poor antenatal care, lack of adequate maternal antitetanus vaccination and unsafe deliveries outside hospitals (2). Neonatal tetanus has been reported to be one of the leading causes of newborn deaths in some parts of the developing world (3). The case fatality rates ranging from as low as 30% to as high as 60% (2). Recent observations have shown that the risk of death from neonatal tetanus may be directly related to poor or inadequate antitetanus vaccination of the mothers (4). The objectives of this Cochrane review (5) were to assess the effectiveness of tetanus vaccine in the prevention of neonatal tetanus and neonatal tetanus deaths, as well as the incidence rates of adverse effects of antitetanus vaccination.

2. METHODS OF THE REVIEW

The authors of the review planned to include randomized and quasi-randomized trials that had compared tetanus toxoid vaccine in humans with placebo, control vaccines or no intervention and trials that had compared any types, dosages or schedules of tetanus toxoid vaccine. The authors conducted an extensive search for all relevant published and unpublished studies between 1966 and 2007 without any language restriction. Two review authors assessed all relevant trials and applied the inclusion criteria. They judged the quality of the studies independently and, where disagreements arose, they were settled them through arbitration by the coordinator of the Cochrane Vaccine Field.

3. RESULTS OF THE REVIEW

Two trials with 95 704 women and 10 560 infants were included in the review. The women had been vaccinated against tetanus and their infants were studied for neonatal tetanus and tetanus deaths. However, the women in the individual trials were not homogenized. Some of the women were pregnant and others were non-pregnant women in the child-bearing age. The authors of the review did not comment on the variations in the characteristics of the participants. Furthermore, the participants had been recruited into the trials irrespective of their antitetanus immunization status.

The first trial, which was conducted in Columbia, had compared aluminium phosphate-adsorbed tetanus toxoid with polyvalent influenza vaccine among women aged 13–45 years. The second trial, conducted in Bangladesh, had compared adsorbed tetanus-diphtheria toxoid vaccine with cholera toxoid among women aged 15 years or more and children aged 1–14 years. While the Columbia trial had randomized the participants to three doses of each vaccine, the Bangladesh trial was less specific about randomization, with one or two doses of the vaccines. In both trials there was no indication whether pregnant women had been separated from non-pregnant women in terms of allocation and analysis of data.

Although, the periods of post-immunization follow-up differed (32 months in Bangladesh and 60 months in Columbia), the periods were long enough to achieve reliable determination of the effects of vaccination on the incidence of neonatal tetanus. The outcome variables in the two trials were similar, but not uniform.

Nevertheless, the review demonstrated that in the Columbia trial, after a single dose, the effectiveness of the vaccine was 43%, with the relative risk (RR) of neonatal tetanus being 0.57 and the 95% confidence interval (CI) 0.26–1.24. However, with 2–3 doses, the effectiveness of the vaccine increased to 98% (RR 0.02; 95% CI 0.00–0.30). In addition, the overall risk of neonatal tetanus after at least one dose of tetanus toxoid was reported as 0.20 (95% CI 0.10–0.40), while the vaccine effectiveness was 80%.

In the Bangladesh trial, the effect of tetanus-diphtheria toxoid on neonatal tetanus cases was not described, but the relative risk of neonatal death after one or two doses of tetanus-diphtheria toxoid in that trial was 0.68 (95% CI 0.56–0.82), while vaccine effectiveness was 32%. This vaccine also prevented neonatal deaths between 4 and 14 days of life with effectiveness of 62%. Neither of the trials in review presented data on the prevalence or severity of side-effects of the vaccines used.

4. DISCUSSION

4.1 APPLICABILITY OF THE RESULTS

Multiple (2–3) doses of tetanus toxoid or tetanus-diphtheria toxoid vaccine need to be administered to the mother to prevent up to 80% of neonatal tetanus deaths. Single doses of the tetanus vaccine are not enough to prevent neonatal tetanus deaths. Since the two included trials in the review were conducted in un-resourced settings, the results of the review are applicable to under-resourced settings.

It is worth noting that the neonatal tetanus deaths persist despite the availability of a safe and effective vaccine. From this it can be postulated that persistence of neonatal tetanus is related to other epidemiological factors rather than low efficacy of tetanus toxoid vaccine. For instance, a recent study in Nigeria revealed that despite expansion of the national immunization programme, the pattern of incidence and mortality related to neonatal tetanus did not change significantly over time (6). This has been attributed to the poor utilization of good-quality obstetric services, including antitetanus immunization and deliveries outside hospitals, which are factors that have remained unchanged over the two periods characterized by different national immunization programmes. Therefore, in under-resourced settings, the full benefits of tetanus vaccinations can only be derived if pregnant women not only receive multiple doses of the vaccine, but also obstetrics care that ensures clean deliveries.

4.2. IMPLEMENTATION OF THE INTERVETNION

Multiple doses of antitetanus vaccine should be administered to women in the child-bearing age as a way of eradicating neonatal tetanus in the developing world. In addition, antitetanus vaccine coverage is likely to increase rapidly if supplemental door-to-door immunization campaigns are adopted in addition to routine clinic-based immunizations (7). Indeed, health education should also emphasize the need to take multiple doses of tetanus toxoid regardless of the pregnancy status of women of child-bearing age. The inclusion of routine antitetanus vaccination in school health services had previously been suggested as a way of increasing the coverage of tetanus toxoid vaccination (2). Health-care workers at all level of health-care delivery should be trained in the technicalities of antitetanus vaccination as they should form the arrowhead of health education drives in communities.

4.3. IMPLICATIONS FOR RESEARCH

It is essential to expand the scope of trials on this topic to include estimations of serum levels of antitetanus antibodies induced by the doses of the vaccine and relate these to the incidence and mortality of neonatal tetanus. This is important in view of the observation that neonatal tetanus and neonatal tetanus deaths occur even among infants of immunized women (8). It will be interesting also to determine the degree of immune response to doses of tetanus toxoid in specific populations. It is also important to study possible interactions between antitetanus vaccines and other events that characterize the prenatal periods, such as malaria chemoprophylaxis, maternal malnutrition, vitamin A deficiency and maternal anaemia. These are particularly important in parts of the world where malaria is endemic and most pregnant women who require antitetanus vaccination also have co-existing malnutrition and anaemia. If interactions truly exist, then it may be necessary to review the subsisting policies guiding antitetanus vaccination with respect to prenatal vaccination. More studies of the epidemiological factors that inhibit appropriate utilization of antitetanus vaccination services in the developing world will also be desirable.

Sources of support: None

References

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  • Fetuga MB, Ogunlesi TA, Adekanmbi AF, Olanrewaju DM. Tetanus among the babies of immunized mothers in Nigeria. Tropical Doctor 2009;39:135-137.

This document should be cited as: Ogunlesi TA. Vaccines for women to prevent neonatal tetanus : RHL commentary (last revised: 1 April 2011). The WHO Reproductive Health Library; Geneva: World Health Organization.

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