Immunisation policies--successes, failures and the future.

Introduction The development of vaccines to prevent infectious diseases is one of the most significant achievements of medical science. Few other interventions, prophylactic or therapeutic, can boast its success either in terms of prevention of morbidity or cost-effectiveness of the measure. Over 80% of the world's children now receive at least three primary immunisations during the first year of life, resulting in the prevention of around three million childhood deaths each year. In North America and Western Europe, deaths from the former childhood killers-measles, pertussis, polio, diphtheria, and tetanus-are now virtually unknown. Much of this success has been achieved with vaccines produced by relatively primitive technology and without a proper understanding of the immunological mechanisms underlying protection. The empirical approach of developing live attenuated vaccine strains of naturally virulent viruses by serial passage in non-human tissue or host was surprisingly successful, as witnessed by the highly effective oral poliomyelitis (Sabin) vaccine. The Sabin strain, selected for its lack of neurovirulence in monkeys (a property which was subsequently confirmed by its administration to Sabin's susceptible wife, two daughters and their three playmates') proved to be an almost a perfect vaccine. It was cheap, effective by the oral route even in very young infants, immunised contacts via faecal/oral spread, and had an extremely low rate of reversion to virulenceabout one per million doses distributed. Poor thermostability was its only major failing. Many years later, when the technique of nucleotide sequencing became available, the relatively few point mutations in the poliovirus genome responsible for attenuation were identified,2 allowing an understanding of the molecular basis of neurovirulence and illustrating the sophisticated genetic engineering that could be achieved by systematic work in an animal model. For bacterial vaccines, the simple process of formaldehyde inactivation of the exotoxins of Corynebacterium diphtheriae and Clostridium tetani proved equally successful, with the resulting toxoids retaining their protective epitopes but losing their toxic activity. The subsequent successful combination of diphtheria and tetanus toxoids with whole-cell pertussis vaccine, and the discovery that aluminium salts acted as an adjuvant, led to the first combined vaccine (DTP) which has been used worldwide to considerable effect for over 50 years. More recently, the development of glycoconjugation technology, which allows polysaccharide to be converted from a T cell independent to a T cell dependent immunogen by covalent coupling to a protein carrier, has extended the range of vaccine preventable bacterial infections in children. With the right choice of carrier protein, saccharides such as the polyribosyl-ribitol phosphate of Haemophilus influenzae type b become immunogenic in children under two years of age, eliciting protective IgG antibodies in serum and inducing immunological memory. In countries where H influenzae type b conjugate vaccines have been introduced, invasive H influenzae type b disease in infants and young children has virtually disappeared.3 Similar technology has now been applied to polysaccharides from Neisseria meningitis group C and Streptococcus pneumoniae and conjugate vaccines containing these antigens are already in clinical trials in children in a number of countries. Apart from such technological achievements, understanding of the epidemiological impact of vaccination programmes has grown, with equal weight now being placed on the implementation strategy and the quality of the vaccine. The global initiative to eradicate smallpox is a good example of what can be achieved with the right strategy. In 1967, when the World Health Organisation (WHO) initiated the eradication programme, there were about 20 million cases of smallpox and around 1.5 to 2 million deaths worldwide. Within 10 years the last wild case had been recorded in Somalia. The lessons learned during the eradication of smallpox are now being applied to poliomyelitis for which there is a WHO target of global eradication by the year 2000. The importance of maintaining high vaccine coverage, supplemented by mass vaccination campaigns to interrupt disease transmission in endemic areas, has been shown in the Americas where the last confirmed case of paralytic poliomyelitis occurred in Peru in August 1991.5 Institution of active surveillance systems to identify and investigate all cases of Immunisation Division, PHLS Communicable Disease Surveillance Centre, 61 Colindale Avenue, London NW9 SEQ