Elsevier

Vaccine

Volume 19, Issues 2–3, 15 September 2000, Pages 167-173
Vaccine

Immunity to diphtheria and tetanus in England and Wales

https://doi.org/10.1016/S0264-410X(00)00184-5Get rights and content

Abstract

The immunity profile of the English and Welsh population to diphtheria and tetanus has been determined by measuring diphtheria and tetanus antitoxin levels for 3088 and 3142 sera, respectively. Time-resolved fluorimetric immunoassayDELFIA was used to measure diphtheria antitoxin levels and an in-house, indirect ELISA to measure tetanus antitoxin levels. More than 80% of those aged between 2 and 20–24 years had protective diphtheria antitoxin levels of 0.01 IU/ml, or greater, and more than 80% of those aged between 4 and 35–39 years had protective tetanus antitoxin levels of 0.1 IU/ml, or greater. Only 29% and 53% of those aged 60 and over were protected against diphtheria and tetanus. Two increases of diphtheria antitoxin levels greater than 0.1 IU/ml and tetanus antitoxin levels greater than 1.0 IU/ml were apparent, starting at 4 and 14 years of age, which correspond with the policy of giving a diphtheria and tetanus toxoid booster on school entry and a tetanus plus low-dose diphtheria toxoid (recently introduced) booster to school leavers. This is the first comprehensive study of diphtheria and tetanus immunity in the English and Welsh population and shows that the accelerated schedule of immunisation, introduced in 1990, has effectively primed immunological memory against both these antigens and that boosting at school entry and at school leaving is effective in increasing levels of immunity.

Introduction

Immunisation against diphtheria, which commenced on a national scale in the early 1940s, has been a tremendous success, and now, diphtheria is a very rare disease in England and Wales [1], [2]. Unlike diphtheria, tetanus is not an epidemic disease, but is acquired through inoculation of wounds with spores of Clostridium tetani. Neonatal tetanus has been of very low incidence in England and Wales [3] and before 1950 active immunisation with tetanus toxoid was virtually restricted to military personnel. Only in 1964 was universal active immunisation officially sanctioned in England and Wales [4]; although, tetanus vaccination had been performed as part of childhood immunisation schedules before this time [5].

In recent years, in England and Wales there have been a number of alterations and additions to the national vaccination programme [6] which could have a significant impact on the immunity of the population to diphtheria and tetanus. With the aim of improving levels of vaccine uptake, an accelerated schedule of diphtheria, tetanus and pertussis (DTP) immunisation was implemented in the early 1990s [7]. In 1994, a low dose diphtheria component was added to the school leavers dose of tetanus toxoid [8]. Very recently, the traditionally used whole cell component of DTP has been replaced by acellular components [9] and meningococcal C conjugate vaccination has been introduced [10]. The meningococcal C conjugate vaccination programme is targeted at pre-school entry and school leaving and is of particular interest because the vaccines used contain either mutant diphtheria toxin, i.e. CRM197 [11] or tetanus toxoid [12].

The object of this study is to show the immunity profile of the English and Welsh population to diphtheria and tetanus using an appropriately selected set of sera. Such an initiative is timely because it will provide a baseline against which to evaluate the impact of the recently introduced meningococcal C conjugate vaccine immunisation programme, particularly in those aged under 18 years.

Section snippets

Study population and study design

The survey was carried out on residual sera from 18 laboratories which had been used for microbiological or biochemical investigations and then submitted to the Public Health Laboratory Service Seroepidemiology Unit during 1996. The minimum number of sera collected per age group was determined from power calculations using age specific estimates of sero-prevalence of antibody to various vaccine preventable infections including diphtheria [13]. The target number of samples were 100 from yearly

Results

Diphtheria and tetanus antitoxin levels were obtained for 3088 and 3142 sera, respectively. The shortfall from a total of 3300 which should have been tested, according to the study protocol was due to insufficient volumes, inappropriate serum samples (grossly haemolysed, contaminated) and non-specific antibody reactivities.

Fig. 1 shows the distribution of (a) diphtheria antitoxin levels and (b) tetanus antitoxin levels by age group. For diphtheria, we have considered antitoxin levels less than

Discussion

This is the first survey to measure both diphtheria and tetanus antibody levels in a large age and sex stratified set of serum samples collected from England and Wales. The diphtheria antitoxin titres obtained have been classified, according to established criteria [17], levels of less than 0.01 IU/ml indicate susceptibility, levels of 0.01 IU/ml to 0.1 IU/ml provide protection against the toxic manifestations of disease and levels greater than 0.1 IU/ml are fully protective. For the tetanus

Acknowledgments

We would like to thank Dr. Louise Hesketh of the PHLS Sero-epidemiology Unit for the supply of sera, Kelly Batey for technical assistance and Dr. Geoff Barnard of the Regional Endocrine Unit, Southampton General Hospital for the europium labelling of diphtheria toxoid.

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