The Pharmaceutical Journal
Vol 269 No 7216 p399-401
21 September 2002

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World Congress of Pharmacy and Pharmaceutical Sciences summary

Partnerships can lead to positive outcomes in vaccination programmes

The successful introduction of meningitis C vaccine in the United Kingdom is an example of a case where successful partnerships between government, the pharmaceutical industry and the general public can lead to positive outcomes in vaccination programs. This was demonstrated by Dr David Salisbury, principal medical officer, Department of Health, UK, when he spoke at a joint scientific and professional session on 4 September.

Meningococcal infection presents either as meningitis, septicaemia or both. Group B infection accounts for 60 to 65 per cent of cases in the UK and no vaccine is available. Group C infection accounts for 25 to 40 per cent of cases. Meningococcal infections are seasonal, exhibiting a peak effect in winter. Cases in Britain increased steadily year on year between 1994 and 1999. Epidemiological data showed that mainly children were affected: one- to three-year-olds and teenagers. Seven per cent of all group B cases died. For group C, teenagers aged 15 to 19 years were at highest risk of dying if they caught the disease. The aim of the vaccination programme was, therefore, not only to prevent the spread of the disease but also to prevent death. Both young children and teenagers must be vaccinated. Deaths from meningococcal infections have made UK headlines leading to public interest and high awareness of the infection in society, said Dr Salisbury.

Partnership and planning

In 1994, the UK Government held a meeting with the pharmaceutical industry to tackle the need for vaccination. A vaccine needed to be developed that was conjugated to induce immunological memory, was suitable for administration at the same time as routine vaccines and could be administered at a young age, when plain polysaccharide vaccines do not work. This meeting, said Dr Salisbury, exposed the dissonance between UK needs and manufacturers' production development strategies. Industry priorities were clearly different from government priorities. However, three companies were developing products along similar lines. Assistance was provided by the Vaccine Evaluation Consortium, set up in the 1990s. This is a Department of Health funded organisation whose main tasks include acceleration of licensing for vaccines.

Dosage strategies tested varied from initial multidose to later single dose administration. Babies and children of all ages were vaccinated in the test phases. Adverse drug reactions were mild. Less than one in 10,000 experienced nausea, dizziness, headache, soreness at the site of injection and rash. Convulsions occurred in one in 100,000 doses and anaphylaxis in two cases per million. There were 14 deaths at a rate of one death per million doses. Seven deaths were due to sudden infant death syndrome; others were due to group B infection, bronchitis, pneumonia, or infantile spasms. Causality in some cases, stated Dr Salisbury, may not be directly attributable to the vaccine.

Cost-effectiveness studies showed that the younger the child vaccinated, the more life years gained. It costs more to vaccinate those aged under one year, and the cheapest age to vaccinate is between one and two years of age. However, it was politically unacceptable to leave under-one- year-olds unprotected.

In 1999, the Health Secretary promoted a nation-wide campaign. The political consequences of supply shortages were deemed acceptable. The Department of Health provided a co-ordinated plan of vaccine allocation using existing data on vaccination programmes in primary care and schools. Vaccines were delivered to general practitioners and schools (in specific waves) according to an agreed timetable. A computerised tracking system had been developed two years previously to track DTP Hib vaccinations for every GP in the UK and these data formed the basis for the meningitis C programme, said Dr Salisbury. Between October and December 2000, 90 per cent of babies, more than 80 per cent of schoolchildren and approximately 70 per cent of those in adult education had been vaccinated. A reduction in cases of over 90 per cent and a similar reduction in deaths has been achieved. Vaccine efficacy varies between 87 and 94 per cent across age groups, with a 61 per cent reduction in cases among unimmunised groups, suggesting evidence of herd effect, ie, reduction of spread of infection.

The future

Effective collaboration between government, industry and key players can produce highly successful vaccination programmes and quicker development of safe, effective vaccines, Dr Salisbury told the congress. The UK was the first country to use the meningitis C vaccine and its use is now planned in many other countries. The problem still facing the industry and government is how to tackle group B infections. This remains a major public health challenge.

Dr Salisbury was asked about the role of the pharmacist. He replied that pharmacists were key players during Department of Health communications. They also had an important role to play in informing doctors, nurses and communities about the disease and the vaccination programme. They were the guardians of vaccines at local level and an integral part of the schools vaccination programs.

When asked about nasal application of meningitis C, Dr Salisbury agreed there is a scientific, theoretical advantage over subcutaneous administration. In practice, nasal administration to babies aged between two and four months was operationally difficult.

Combination vaccines

Patrick Poirot, Aventis Pasteur MSD, France, suggested that combination vaccines are an essential tool for immunisation programmes. To date, there are around 20 to 26 diseases that are preventable through vaccination. He emphasised that it was important to differentiate between different types of combination vaccines. A "true" combination vaccine is one where monovalent vaccines treating different diseases are combined into a multivalent form. A strong coherence between the different valences is compulsory. Vaccines come in tri-, tetra-, penta- or hexavalent forms. Current combined vaccines are either whole-cellular or acellular pertussis formulations.

Parents have strong feelings about their children receiving so many injections during their early years, said Mr Poirot. Without combined vaccines, infants could receive up to 50 single injections. Combined vaccines reduce the overall number administered and are therefore regarded as child- and parent-friendly. Medical staff find them time-saving and convenient. There are limited possibilities when vaccinating children and combined vaccines get around the problem of short deadlines. They simplify the total vaccination calendar and improve vaccination compliance. This leads them to be cost-effective in comparison with single vaccines. Infant vaccinations are the primary market for combined vaccines. In adults the market is limited, concentrating on travellers and the elderly.

Formulation and production of combined vaccines should be regarded as equivalent to a new development with regard to the time and resources required, according to Dr Poirot. It was not as simple as mixing two existing preparations or antigens. Ionic buffer strength, pH, adjuvant properties, antigen properties and order of mixing all affect the stability of the final product. The preparation of one batch of hexavalent vaccine may take anything between 10 and 18 months. Around 400 quality control tests are required — the risk of failure in any of these tests puts back the whole process. Apart from the technical issues, the combined vaccine must be equivalent in performance to the single component vaccines with regard to immune response, efficacy and tolerance. Post-market surveillance is particularly challenging with combined vaccines because it is difficult to attribute an adverse drug reaction to a single component. Economically, vaccine development costs must not be more expensive than the development of other products. The market value of the combined vaccine plays an important part in the investment decision.

Dr Poirot concluded by saying that the vaccine industry is facing a supply problem. Production capacity is limited because demand in terms of doses is far exceeding supply. Industry and other stakeholders have underestimated the huge success of vaccination programmes. Time is the rate limiting step — validation and quality control tests are time-consuming. Precision planning, as with the meningitis C example allows anticipation of demand and manufacture.

New formulations simplify delivery

Dr Teresa Aguado, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland, informed participants about current challenges in vaccination strategies and vaccine delivery. Six major diseases are prevalent killers in the under-fives, mainly in developing countries: acute respiratory infection, AIDS, TB, malaria, measles and diarrhoea. Vaccination schedules need to be optimised. Better surveillance of mass campaign effects and the epidemiological impact of vaccination is required. Alternative delivery methods would lead to simpler and safer vaccination methods, she said. Temperature stable vaccinations could logistically improve access to full vaccination coverage globally. Needle-free vaccines would improve compliance because needle-phobia would not be such a problem. Technological advances currently under investigation include jet injectors, pre-filled devices, transdermal routes and mucosal routes (nasal, oral, genital). Each has its own challenges such as dose standardisation, tolerance, need for cold chain, etc. In an effort to improve vaccine stability in different temperatures, thermostabilisation via the use of sugars is being investigated. Sugars are particularly favoured because they are inert, thermostable, have a controllable particle size and are perfectly soluble in moisture. Devices such as aerosols (eg, for 'flu) and nebulisers (eg, for measles) have been used to test mucosal delivery. Preliminary studies with nebulisers have shown good results in primary measles immunisations in infants and young children with no increase in adverse drug reactions. More tests are required regarding particle size and dose distribution, for example.

More vaccinations with different delivery routes will come in the future but it is difficult for the industry to switch production lines for existing vaccines. This is easier for newer vaccines under development, eg, malaria and TB. Dr Aguado urged manufacturers in developing countries to capitalise on this niche market of opportunity and benefit their host country.

Are vaccines really safe?

Dr John Clements, Vaccines and Biologicals, WHO, Geneva, told the congress that communication, thinking and emotions all play a vital role when the public make a decision about vaccines. The Erice Declaration 1997 states "all evidence needed to assess and understand risks and benefits must be openly available. Constraints on communication must be recognised and overcome". The problem is, vaccines are often administered to children, who are not decision makers. Also, when receiving the vaccines they are healthy, so the risk-benefit equation is difficult to assess. The media usually do their best to portray risks and benefits in a balanced way, ie, risk of vaccine damage is equal to the risk of the disease itself. The reality is very different, according to Dr Clements. He portrays the risk of vaccine damage as small and quantifiable whereas the risk of non-vaccination is high. He emphasised that there is no way to bring a balance in this equation.

Usually, public opinion has already been informed before the health professional enters the scene. Examples of this have been scares surrounding bovine spongiform encephalitis, mobile telephones, atomic power stations, overhead power cables, etc. Where vaccines are concerned, the public usually ask "Are they safe?", "Whom should we believe?" and "Is it better to risk catching mild disease rather than suffer major side effects to the vaccine?". The media, governments, independent scientists, medical press, anti-vaccine lobby, and international bodies such as WHO all play a part in informing the public about vaccines. Dr Clements asked: "Which play the greatest part? Which of these will take responsibility if there is a lack of confidence in vaccines leading to a major public health crisis?" He suggested that it should be a corporate responsibility. Information has to be given in the correct form, in the correct amount at the right time. During an epidemic, the public are not interested in risks and side-effects. In uneducated patients, information overload can have negative consequences. There is no justification for not providing all the facts but how you provide it depends on the target group and social setting. Professional honesty is a highly valued commodity. Any loss of trust has widespread implications for the whole health care profession.

Communication challenge

There is a huge communication challenge for all stakeholders. Health professionals have a duty to be fully informed and present information in an unbiased way. Researchers have a duty to present their reports honestly and make the limitations clear. The medical press should ensure peer review of articles and be prepared to publish negative results. The media has a responsibility to understand the "balance" equation and not capitalise on political debates that may cost lives. The concepts of risk and causality are difficult to understand. The public and anti-vaccine lobby groups need to be engaged in debate.

He emphasised relationships with general media should be built upon continu-ously. "It is too late during a crisis to expect the media to give you a fair hearing. This is a skill outside a health professional's comfort zone but needs developing."

Dr Clements explained that the MMR and autism debate is a case in point. This continuing debate is an excellent example of science saying one thing and "mavericks" saying another. Society chose to go with the maverick. The community pharmacist's role is to deal with society's anxieties about vaccine safety and provide correct, unbiased information about vaccines for travellers, general vaccinations and epidemics. They are an excellent partner in the community – the scientist in the high street.—Contributed by Sonia Sanghani.