Effect of Tetanus Toxoid Vaccine on Neonatal Tetanus

Evaluation of the effect of Tetanus Toxoid vaccine on neonatal tetanus

Clinical scenario

Tetanus is a vaccine preventable disease caused by a ubiquitous spore-forming bacteria called Clostridium tetani (reference need). Due to its ubiquity, the disease cannot be eradicated (Roper et al. 2007). Tetanus that occurs in neonates between 3-28 days of life is termed neonatal tetanus (CDC, 1997) and the most common nidus of infection in neonates is through the freshly cut umbilical cord (Bennett et al. 1996; Roper et al. 2007). Substantial progress has been made towards the elimination of maternal and neonatal tetanus (MNT) by the WHO initiative, although it still remains a major problem in more than 30 developing countries (figure 1) (WHO, 2015).

Figure 1. The global map sowing the advancement towards the elimination of maternal and neonatal tetanus.

Source: WHO. (2015). [Online].

http://www.who.int/immunization/diseases/MNTE_initiative/en/index4.html

Developed countries such as the United States of America, England and Denmark, have long ago eliminated tetanus linked neonatal deaths compared to developing countries (Pascual et al. 2003; Simonsen et al. 1987; Rushdy et al. 2003). Haws et al. (2007) mentioned that in areas where the prevalence of neonatal tetanus is common, vaccinating women against tetanus during pregnancy is likely to prevent the disease. Neonatal tetanus still remains one of the leading causes of infant mortality in many developing countries despite the fact that tetanus vaccine has been available for years (Stanfield et al. 1984). Hence, the aim of this critical appraisal is to evaluate the effect of tetanus toxoid vaccine given to pregnant women to provide effective protection and reduce deaths from neonatal tetanus in comparison to no vaccine.

Focused Clinical Question

In pregnant women in developing countries, does vaccination with tetanus toxoid vaccine provide effective protection and reduced death from neonatal tetanus in comparison with no vaccine?

PICO used to guide the search strategy

Patient: Pregnant women, developing countries
Intervention: Tetanus Toxoid Vaccine
Comparison: No vaccinationor best available alternative
Outcome(s): Effective protection of neonates, reduced death from Neonatal tetanusafter vaccination with Tetanus Toxoid

Databases searched

Search terms used

Limits Used

PubMed

Web of Science

Cochrane library

World Health Organisation Regional Databases

Tetanus immunisation/

Pregnant women

Neonatal Tetanus

Tetanus toxoid vaccine pregnancy

Neonatal Tetanus

Published 2000-2015

Filters: Meta-analysis, Cross-sectional study, Systematic Review

Published 2007-2015

Filters: Article, Review

Systematic Review

Table 1: Search Strategy

Inclusion and Exclusion Criteria

Inclusion Criteria

Abstract and author of published work available
Freely accessible online
Published in English
Studies carried out in developing countries
Directly linked to effective protection and reduced death from neonatal tetanus and tetanus toxoid vaccination
Pregnant women at any period of gestation, married and unmarried
Vaccination with tetanus toxoid

Exclusion Criteria

No abstract or author of published work
Not a study or trial
Not freely accessible online
Published in any other language
Studies carried out in developed countries
Not directly linked to effective protection and reduced death from neonatal and tetanus toxoid vaccination

Table 2: search and screening results

Search terms and PubMed Web of Science Cochrane Library

Screening used

“Neonatal Tetanus” 1037 371 52

“Tetanus toxoid

Vaccination” 3882 856 454

“Tetanus toxoid

vaccine pregnancy” 721 45 17

After abstract

Screening 8 0 3

After full

Articles

Screening 2 0 1

Total number of studies = 3 (Blencowe et al., 2010; Maral et al., 2001 and Demicheli et al., 2013).

Table 3: CASP screening tool for the appraisal of two Systematic Reviews and one Cross-sectional Study

CASP Questions Authors and study design

Blencowe et al., Maral et al., Demicheli et al.,

2010 Systematic 2001 Cross- Systematic

Review Sectional study* Review

1. Did the study address a YES

clearly focussed question?

2. Did the authors look for the YES

right type of papers?

3. Do you think all the important, YES

relevant studies were included?

4. Did the reviews authors do enough YES

to access the quality of the included

studies?

5. If the results of the review have been YES

combined, was it reasonable to do so?

6. What are the overall results of the

review?

7. How precise are the results?

8. Can the results be applied to the local

population?

9. Were all important outcomes considered?

10. Are the benefits worth the harms or YES

costs?

*A cross-sectional appraisal tool does not exist, therefore Maral et al., 2001 was appraised using the systematic review appraisal tool.

Exclusions

Summary of best evidence – Blencowe et al., 2010 Systematic review

Aim/Objective of the Systematic review:

To evaluate the effect of Tetanus Toxoid vaccination of pregnant women or women of child bearing age on neonatal tetanus mortality.

Study Design

Search Strategy

A range of appropriate databases were used such as PubMed, EMASE, Cochrane Libraries and World Health Organisation Regional Databases. Suitable search terms were used such as ‘Neonatal Tetanus, Tetanus Toxoid, Neonatal Mortality and Women’. Publications in any language were also included.

Selection Criteria for inclusion of studies

The PICO format (Patient, Intervention, Comparison and Outcome) was used in this review to identify the studies to be included as follows:

Population – Neonates

Intervention – At least two Tetanus Toxoid vaccine doses

Comparison – Neonates born without Tetanus Toxoid vaccination

Outcome – Mortality from Neonatal Tetanus

Randomised trails and observational studies meeting the above criteria’s were considered in this review.

Methods

A systematic review of various databases was carried out to identify suitable studies meeting inclusion criteria
Standardised abstraction forms were used for each outcome of interest for studies meeting the inclusion criteria
Studies not meeting the inclusion criteria, studies which only reported serological outcomes and duplicate reports of studies or trails were all excluded
Quality of individual studies and evidence were evaluated according to the CHERG version of the GRADE method to generate an approximate calculation of the effects in reducing neonatal mortality
A meta-analysis was carried out using STATA version 10.0 statistic software and stated the mantel-haenszel pooled relative risk and corresponding 95% confidence intervals (CI)

Findings

Two studies which had no heterogeneity between them (p=0.16) i.e. a high-quality randomised controlled trial and a well-designed cohort study with adjustment for publication bias in its analysis, were joined into one meta-analysis to give an estimate of relative risk (RR)= 0.06 (95% CI 0.02-0.2) (Fig. 1). While, three case-control studies each with adjustment for publication bias showed a protective effect of two tetanus toxoid injections during pregnancy (odd ratio (OR) = 0.05 (0.005-0.4); OR=0.1 (0.03_0.4); OR=0.2 (0.03-0.7).

Overall result

A 94% reduction in neonatal tetanus mortality (95% CI 80-98%). The confidence interval of 95% for these results appear to be accurate.