a PHLS Sero-Epidemiology Unit, Immunisation Division, Communicable Disease Surveillance Centre, 61 Colindale Avenue, London NW9 5EQ, UK.
b PHLS Sero-Epidemiology Unit, Preston Public Health Laboratory, Royal Preston Hospital, PO Box 202, Sharoe Green Lane, Fulwood, Preston, Lancashire PR2 9HG, UK.
c PHLS Sero-Epidemiology Unit, Public Health Laboratory Service North West, Directorate Office, Vicarage Lane, Fulwood, Preston, Lancashire PR2 8DW, UK.
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Abstract |
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Methods Residual sera are collected in participating laboratories and sent to a central store where they are irrevocably unlinked from identifying data. A unique identity number is assigned to each serum and details of age and sex are collated on a database. The sera are accessed for testing as required.
Results The results of recurring and other surveys performed over the last ten years are presented. These demonstrate that opportunistic serum samples are an ideal resource for serological surveillance programmes.
Conclusions The serological surveillance programme has provided past exposure profiles for many infections. These data have resulted in a number of national policy changes and have been instrumental in shaping the UK vaccination programme.
Keywords Serological surveillance, immunization, vaccine preventable diseases, mathematical modelling, MMR
Accepted 27 August 1999
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Introduction |
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The first age-stratified serological survey of antibody to measles, mumps and rubella (MMR) in England and Wales was conducted in 1986/87,11 prior to the introduction of MMR vaccine in 1988. We describe the development of the serological surveillance programme over the following ten years, presenting its main results and their implications for disease control.
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Methods |
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For each serum, the age (or date of birth if available), sex, date of specimen and laboratory number are entered on a data sheet in the collecting laboratory. Sera and the accompanying documentation are forwarded to Preston PHL where each serum is assigned a unique identity number and the laboratory numbers removed so that the patients are no longer identifiable. This irrevocably unlinks the serum from any patient identifying data. Sera are stored at 20°C in dedicated freezers at Preston PHL. The data sheet is then forwarded to CDSC where the information is entered onto a central database.
Each year target numbers of sera (stratified by age and sex) are collected in the age groups 024 years. Every five years (1986/7, 1991 and 1996) sera are collected across the entire age range (although any sera provided in the intermediate years from older age groups are not discarded). Figure 2 shows the number of sera collected each year by age group. For each survey the required number of samples for each stratum (e.g. age group) are randomly selected from those available. The identification numbers are sent to Preston PHL where the majority of the testing (largely automated since 1994) is performed. Results are downloaded directly from the auto-analyser and sent to CDSC in computer files, where they are incorporated into the database and analysed.
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Results |
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Measles, mumps and rubella
The measles, mumps and rubella surveys have been performed every year since 1986/87 (Table 1). The results have played a crucial role in shaping the UK national vaccination policy, most notably in identifying the need for a national vaccination campaign in 1994 to prevent a potential measles epidemic.13,14 As a result 7 million children aged 516 years were vaccinated in November 1994, 92% of all children in this age group. The impact on immunity to measles and rubella in the target populations was confirmed by surveys using samples taken before and after the campaign.15 Following this, and the subsequent introduction of a second dose of MMR vaccine in 1996, the incidence of measles, mumps and rubella is low. It will be important to continue serological surveillance to monitor antibody prevalence, particularly in cohorts not vaccinated in the campaign (young adults and young children).
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The availability of archived sera is particularly valuable in investigating infections with long-term trends in their incidence (Table 3). For example, testing two cohorts of sera from 1014 year olds collected 8 years apart has demonstrated a decline in the prevalence of infection with herpes simplex virus type 1 (HSV-1) (paper in preparation). This is caused by a decline in the incidence of infection in childhood and may contribute to changes in the epidemiology of genital herpes in adults.
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Discussion |
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The UK has a well-developed NHS with free access to health care for all. This limits the selection bias for UK residual sera, which is likely to be less than that for residual sera obtained in countries where access to health care is more limited. Furthermore, the sera have the advantages of being cheap and easy to obtain. Importantly they also avoid additional patient discomfort, particularly in young children. In view of the comprehensive diagnostic service that each laboratory offers, substantial differences in the reasons for which sera were submitted are unlikely, either over time or between laboratories. Therefore valid regional and temporal comparisons can be made. Regional comparisons have been facilitated by the increase in the number of participating laboratories.
In other countries (e.g. the Netherlands,23 the US24) surveys have been conducted using sera specifically donated by people randomly sampled from the population. This has the advantage of allowing detailed risk factor information to be obtained, but any gain in the representativeness of the sera comes at considerable financial cost. There is also no guarantee that the sera will be representative because of the potential for participation bias. Even follow up of non-responders cannot completely eliminate or correct for this bias.
The major limitation of the programme in England and Wales is the lack of any data on ethnic group or country of birth. This is particularly problematic when studying diseases that are far more prevalent in other countries, e.g. hepatitis B. One solution would be to conduct occasional cross-sectional surveys on a smaller scale in which the requisite demographic information was collected.
The relatively simple methodology of the serological surveillance programme in England and Wales makes it transferable to other populations and countries. In countries with less developed health care infrastructures, alternative sources of sera could include those taken in accident and emergency departments.
Interaction with mathematical modelling
The interaction of serological surveillance with mathematical modelling has been particularly fruitful: surveys have provided better baseline data for mathematical models, which have been used to interpret the results of later serological surveys. The force of infection (the rate at which susceptibles acquire infection)18 can be estimated from the age-specific antibody prevalence in an unvaccinated population, provided there is no long term trend in the incidence of infection. Contact rates between age groups, which can be estimated from the age-specific force of infection in an unvaccinated population, are fundamental parameters of mathematical models of disease transmission,25 and reflect the potential for transmission of infection within the population.
Introduction of vaccination will change the prevalence profile (the age-specific prevalence of antibody) and the force of infection in a population, but not the contact rates (although, over long periods of time, contact rates may be affected by social changes within a population). Contact rates derived from pre-vaccination prevalence profiles can therefore be used to interpret the profiles obtained after vaccination is introduced.14 Each serological profile can be summarized by a single parameter: the reproduction number, R. R is the number of secondary cases produced by a typical primary case; thus potential for an epidemic exists if R is greater than one. R is determined by the level of susceptibility in each age group and the contact rates within and between age groups. The sensitivity of R to the contact rates can also be explored. This method was applied to the serological results for measles, predicting a potential measles epidemic14 that was prevented by the 1994 national vaccination campaign.
Interaction with other surveillance programmes
Comprehensive surveillance of vaccine preventable infections requires data from several sources. Serological surveillance complements but cannot replace surveillance of vaccine coverage and disease incidence (both clinical diagnoses and laboratory confirmed cases). For example, serological surveillance cannot rapidly detect changes in vaccination coverage, which can only be achieved by direct monitoring of coverage itself. Similarly, it cannot identify disease outbreaks or short term trends in disease incidence. However, disease incidence data yield little information on the epidemiology of infection if many infections are asymptomatic (especially if the proportion asymptomatic changes with age) or are clinically misdiagnosed. Furthermore, the absence of cases in a population reveals little about the potential for cases in future. Therefore, serological surveys are an important element of the surveillance of vaccination programmes.
Influence on vaccination policy
Serological surveys provide baseline data on the distribution of immunity to infection within a population. They are particularly valuable for evaluating the need for and the planning of new vaccination programmes and supplementary measures such as mass vaccination campaigns. Identifying the cohorts most susceptible to infection enables the intervention to be targeted to achieve maximum effect with the available resources.
The serological surveillance programme in England and Wales has directly influenced national vaccination policy. Examples include the 1994 measles and rubella campaign; the introduction of a second dose of MMR at 4 years of age;26 and the decision not to implement a universal hepatitis B vaccination programme. As vaccination programmes succeed in eliminating infections, monitoring immunity of the population through serological surveys will assume even greater importance to ensure a scientific basis for decisions about national vaccination policy.
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Acknowledgments |
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References |
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