The future of the national immunisation programm: towards a programme for all age groups

Health Council of the Netherlands. The future of the national immunisation programme: towards a programme for all age groups. The Hague: Health Council of the Netherlands, 2007; publication no. 2007/02.

An appropriate moment to consider the future of the NIP

Since 1957, Dutch children have been vaccinated against infectious disease through the National Immunisation Programme (NIP), usually at clinics for infants and toddlers. The programme prevents a great deal of disease and death. Initially, vaccination was provided against diphtheria, whooping cough, tetanus and polio. Later, the programme was extended to also provide protection against measles, German measles, mumps, hepatitis B, and infection by Haemophilus influenzae type b, meningococcus C and pneumococci.
Since 2005, management of the programme has been the responsibility of the Centre for Infectious Disease Control (Dutch initials: CIb), part of the National Institute of Public Health and the Environment (RIVM). The Netherlands Vaccine Institute (NVI) produces or sources the vaccines used for the Programme. Finally, the Health Council plays an advisory role in relation to all these activities. The Council identifies and assesses scientific information about vaccination and makes appropriate recommendations regarding the scope and content of the NIP.
The programme’s fiftieth anniversary provides an appropriate opportunity to review the range of vaccinations provided, and to consider the NIP’s future. After all, neither science in general nor epidemiology in particular stands still. In recent years, for example, various new vaccines have become available, raising a number of important questions.
Is it desirable to continue providing all the vaccinations currently included in the programme? What additional vaccinations should be considered for future inclusion? To answer these questions, it is helpful to begin by considering the past: what has the programme achieved to date? It is also desirable to have an assessment framework: what are the grounds for inclusion in the NIP? A clear set of criteria is required. Once defined, such criteria can be used to arrive at transparent rational decisions regarding and priorities for the future of the NIP.

NIP prevents a great deal of disease and death

The NIP makes a very considerable contribution to the prevention of death and disease among children. The introduction of general vaccination has virtually eliminated death from polio, diphtheria and infection by Haemophilus influenzae type b and meningococcus C. The recently introduced vaccination against pneumococci is also expected to have a considerable effect on mortality.
The programme’s impact on the disease burden is also clear. Since the introduction of general vaccination, polio epidemics have been rare and confined to non-vaccinated pietistic reformed Christian communities. Diphtheria and tetanus are all but eradicated from the Netherlands, and measles is now very unusual. The number of hospital admissions due to congenital rubella syndrome has fallen from forty in 1980 to less than one a year since 1987. Vaccination against mumps, also introduced in 1987, has also been very successful. Prior to the provision of mumps vaccine through the programme, between three hundred and eight hundred children were being admitted to hospital with mumps-related meningitis each year. Today, such cases occur only sporadically.
Following the introduction of vaccination against Haemophilus influenzae type b in 1993, invasive infections fell sharply, from around seven hundred a year to twelve in 1999. Since then, however, the number has edged back up again, to forty-nine in 2004, possibly because of a decline in the number of natural re-infections. In other words, the Hib vaccination is effective, but further research is required into its long-term protective effect and interaction with other vaccinations.
The addition to the programme of vaccination against meningococcus C, in 2002, has similarly led to a marked decline in invasive infections. Although the impact of the newly introduced vaccination against pneumococci is not yet known, it is expected to have major benefits both for the children who receive it and, indirectly, for adults.
Vaccination against hepatitis B is now successfully provided to two population groups through the NIP: children whose mothers carry the virus and children with at least one parent from a country where hepatitis B is prevalent. In both cases, the result has been the alleviation of the considerable disease burden associated with chronic infection and the existence of carriers within the population.
Where whooping cough is concerned, the situation is more complex, although here again a great deal of illness and also deaths have been avoided by vaccination. After a prolonged period in which the vaccination was very effective, its effectiveness has been declining since the 1990s. As a result, there have been occasional whooping cough epidemics in the Netherlands. In response, a new acellular whooping cough vaccine was introduced in 2005. A problem is that the protection afforded by vaccination against whooping cough lasts only six to eight yeas. It is unclear what additional measures should be taken to protect very young infants who have yet to begin or complete the vaccination programme. Such infants form an important population group in this context, since they are more vulnerable than other age groups if they contract the illness.

Adverse reactions relatively uncommon

The Netherlands has what is known as a passive system for the registration of adverse reactions to vaccination through the NIP. From the data collected, it is apparent that the vaccinations provided rarely, if ever, trigger serious adverse reactions (i.e. death, serious neurological phenomena or permanent physical injury). The data on less serious transient adverse reactions are less reliable, since such reactions often go unreported.
Since 2004, active focused efforts have been made to determine the frequency of adverse reactions. The proper study of such reactions is particularly important for the acquisition of reliable data concerning the less serious transient phenomena associated with vaccination. It is also valuable as a means of assessing the level of reporting through the established registration system and answering specific questions, such as the effect of changing a particular vaccine.

A high vaccination rate remains important

At present, the vaccination rate achieved by the NIP is more than 95 per cent. However, there are clear geographical differences. For example, in parts of the country with high concentrations of pietistic reformed Christians, some of whom have conscientious objections to vaccination, the vaccination rate is well below the national average.
Such clusters of non-vaccinated people have become very important in relation to the epidemiology of polio, measles and German measles in the Netherlands. The reason being that where the vaccination rate is below 90 to 95 per cent, epidemics are possible. Since 1990 there have been epidemics of polio (1993), measles (1999-2000) and German measles (2004-2005) in parts of the Netherlands with significant pietistic reformed Christian populations.
It is not unreasonable to fear that further such epidemics might occur in the future. Such epidemics could lead to infection spreading to other population groups that are not well protected. There is also a risk that contact between Dutch pietistic reformed Christians and similar communities in other countries could result in the reintroduction of a micro-organism that has been eliminated from the Netherlands. In the past, such contacts have certainly resulted in the communication of polio, measles and German measles from the Netherlands to communities in other countries following localised outbreaks here.

New target groups require consideration

The NIP was originally set up to combat childhood illnesses. With good reason, the programme continues to focus primarily on the vaccination of children. However, the developments surrounding whooping cough have illustrated that older children and adults can also play a key role in the spread of pathogens. It is therefore pertinent to ask whether and, if so, to what extent the vaccination of older children and adults is desirable as well.
Consideration should additionally be given to the question of what constitutes an appropriate period of protection. May a vaccinated individual reasonably expect lifelong protection? In practice, the period of protection is often shorter, but under the present circumstances the risk to adults is too small to justify universal revaccination. In the future, however, that situation may change.
Another shift in emphasis evident within the programme has been the increasing focus on older people. Influenza vaccination is already provided for older people, and it is likely that there will soon be a vaccine suitable for protecting this population group against shingles.
In the future, the availability of vaccines against sexually transmissible diseases may warrant the immunisation of other population groups as well. Such vaccines are best given at the age of eleven or twelve. A vaccine against human papilloma virus, which plays an important role in the development of cervical cancer, is already available.
The extent of the realignments and their implications for selection of the NIP’s target groups are not entirely clear. However, it seems probable that the NIP will increasingly become a programme for all age groups.

Greater understanding of the immune system opens the way for additional vaccines

In the past, use was made of vaccines that had been found to work in practice, without it necessarily being clear how they worked. Nowadays, a lot more is known about the immune system, and this knowledge can be used in the development of vaccines. Developers can now draw on DNA techniques (genomics) and protein chemical techniques (proteomics). Information technology is also important in the search for antigens that could form the basis for new vaccines. Furthermore, certain interesting discoveries have recently been made regarding the way the innate immune system works.
Nevertheless, in many instances not enough is known about the immune system to support vaccine development. It has not so far been possible, for example, to create vaccines against diseases that under natural circumstances do not lead to the acquisition of effective immunity. Medical science is presently able to provide vaccines primarily against diseases that naturally result in the acquisition of long-term immunity.
Increasing scientific knowledge has, however, provided answers to various key questions. There is no convincing evidence that allergic conditions have become more common as a result of vaccination. Indeed, research designed to test the ‘hygiene hypothesis’ has yielded no evidence that the immune system can be compromised by lack of exposure to certain infectious diseases. It is also now known that the immune system is quite capable of coping with very large numbers (thousands) of antigens. There is therefore no reason to suppose that the immune system can be overloaded or otherwise adversely affected by exposure to different antigens, as happens in the NIP. However, it may be that some vaccines are less effective when several are administered together.

Good public information essential

In recent years, a great deal of effort has been put into the provision of public information via leaflets, websites and outreach activities. It is of particular importance that the vaccination rate is not allowed to decline.
A decline is a real danger as the illnesses against which protection is provided become less familiar, and the perception that a health risk would exist without vaccination consequently fades. If this in turn were to result in a lower vaccination rate, the programme could become the victim of its own success. Another consideration is that people nowadays obtain information from a variety of sources and are increasingly inclined to make their own judgements. It is important that information about the NIP is geared to this changing setting. This implies clear communication of the advantages and disadvantages of participation and therefore the availability of well informed and well trained care practitioners.
In this context, it is also important to conduct systematic, regular research into public willingness to submit to vaccination. How receptive are people in different population groups – e.g. well-educated parents – to consent to (their children’s) participation? What factors are influential in this regard? Where new communication strategies are adopted, their effectiveness in use should be monitored.

New assessment framework to support informed decision-making and prioritisation

The protection of the public and society against serious infectious disease by vaccination: this is the NIP’s stated general objective. There are three ways of realising this objective.
The first is the eradication of disease. This is feasible where certain illnesses are concerned (as seen with polio and smallpox), but not in all cases. Where eradication is not possible, the achievement of group or herd immunity is the next option. This involves achieving a level of immunity within a population, such that an infectious disease has very little scope to propagate itself, even to non-immunised individuals. To this end, it is necessary to achieve a high general vaccination rate. If this second strategy is not feasible either, the third option is to protect as many individuals as possible.
Attainment of the programme’s general objective depends on making appropriate decisions about the vaccination of particular target groups. To date, there has been no standard national or international framework for the assessment of vaccination options. This shortcoming has now been corrected by definition of the following seven criteria for the provision of a given form of vaccination for a given group:

1 The infectious disease causes considerable disease burden within the population.
- The infectious disease is serious for individuals, and:
- The infectious disease affects or has the potential to affect a large number of people.

2 Vaccination may be expected to considerably reduce the disease burden within the population.
- The vaccine is effective for the prevention of disease or the reduction of symptoms.
- The necessary vaccination rate is attainable (if eradication or the creation of herd immunity is sought).

3 Any adverse reactions associated with vaccination are not sufficient to substantially diminish the public health benefit.

4 The inconvenience or discomfort that an individual may be expected to experience in connection with his/her personal vaccination is not disproportionate in relation to the health benefit for the individual concerned and the population as a whole. 

5 The inconvenience or discomfort that an individual may be expected to experience in connection with the vaccination programme as a whole is not disproportionate in relation to the health benefit for the individual concerned and the population as a whole. 

6 The ratio between the cost of vaccination and the associated health benefit compares favourably to the cost-benefit ratio associated with other means of reducing the relevant disease burden. 

7 The provision of vaccination may be expected to serve an urgent or potentially urgent public health need.

Provision of all present vaccinations should be continued

All the vaccinations currently provided through the NIP have been assessed against the seven criteria. All were found to satisfy the criteria and their provision should therefore be continued.

New vaccines should be included

The committee has assessed the merit of providing various age groups with vaccination against each of a variety of conditions in the context of a public vaccination programme. Consideration was thus given to: the vaccination of young children against chicken pox, invasive meningococcus B infection, influenza, respiratory syncytial virus infection, intestinal rotavirus infection, tuberculosis, hepatitis A, smallpox, gastrointestinal ulcers and stomach cancer caused by Helicobacter pylori, hepatitis C, group A haemolytic streptococcus infection and Lyme disease; the vaccination of pre-pubescent children against human papilloma virus infection, herpes simplex type 2 virus infection, cytomegalovirus infection, HIV/AIDS infection, pelvic inflammatory disease caused by Chlamydia trachomatis and gonorrhoea; the vaccination of women who hope to have children against group B haemolytic streptococcal infection; the vaccination of older people against influenza, shingles and invasive pneumococcal infections. The most appropriate age for universal vaccination against hepatitis B has yet to be ascertained.
In fifteen of the twenty-three cases, the committee concluded that the disease burden was considerable and that provision of the vaccination in a public programme would therefore be desirable. However, in no case – even where a vaccine is already available – is the committee presently prepared to make an unqualified recommendation that vaccination be included in the programme. Where chicken pox, hepatitis B, intestinal rotavirus infection and cancer resulting from human papilloma virus infection are concerned, the committee believes additional analysis is required in the short term in order to determine the importance and urgency of providing vaccination.

Research and training can enhance implementation of the programme

The NIP should meet high standards, not only in terms of its effectiveness and safety, but also in terms of its implementation. To this end, the committee has made a number of recommendations concerning monitoring and effect investigation, concerning research into adverse reactions, public information and communication, concerning the conditions for research projects in the NIP population, and concerning initial and in-service training.