VACCINATION

The Current and Future Role of Vaccination for Preventing Infective Diarrhoeal Disease

The Current and Future Role of Vaccination for Preventing Infective Diarrhoeal Disease

In developing countries diarrhoeal diseases remain a major cause of mortality in childhood with at least three million children dying from diarrhoea each year. Control programmes focusing on case management have been successful in reducing the mortality by about one million a year since the early 1980s. However, further progress is slow and diarrhoeal-disease morbidity needs to be reduced.

Vaccination is a potential means to reduce both mortality and morbidity associated with diarrhoeal diseases. Considerable progress has been made in the development of candidate vaccines against major enteric pathogens. Both live and non-live oral cholera vaccines have become licensed products and a locally produced killed cholera vaccine has been successfully assessed in a large field trial in Vietnam. An oral shigella vaccine has reached efficacy trials and a prototype vaccine against enterotoxigenic Escherichia coli has entered phase I trials.

However, except for use in specific target areas or populations, incorporation of these bacterial vaccines into public-health immunisation programmes is not in sight. To become a credible intervention, vaccines against diarrhoeal diseases will not only have to be efficacious, but also affordable and cost-effective in comparison with other potential interventions, including promotion of breast feeding, provision of soap (and water) for handwashing, or improvements of infrastructure for safe water and sewage disposal.

In comparison with, for example cholera vaccination, rotavirus vaccination stands out as a potentially cost-effective intervention, and rotavirus disease might be the best case among diarrhoeal diseases for prevention by immunisation. Rotavirus infection is responsible for more diarrhoeal disease -associated mortality (about 600 000 deaths a year) than any other single agent. While most of these deaths are in the developing world, rotavirus is also an important pathogen in developed countries. Only access to health-care facilities and effective case management prevents more deaths occurring.

In fact, improvement of hygiene which has eliminated or reduced bacterial diarrhoea in developed countries has had little impact on rotavirus infection. This experience suggests that rotavirus diarrhoea cannot be controlled by hygiene measures, making the case of rotavirus vaccination even more compelling for developed and developing countries. After some 15 years of trials, at least one rotavirus vaccine is close to being licensed. As a result, rotavirus vaccine will soon be considered for incorporation into immunisation programmes in Western Europe and USA.

Natural immunity for rotavirus

There is a strong case for build-up of natural immunity against rotavirus in the first years of life. In developed countries clinically significant rotavirus gastroenteritis seldom occurs twice in the same child. In Mexico it takes at least two clinical or subclinical rotavirus infections to achieve clinical protection against severe rotavirus diarrhoea and three infections for protection against any diarrhoea caused by rotavirus infection.

While repeated exposures are necessary to induce sustained protection, it is encouraging that symptom-free rotavirus infections can also result in protective immunity. In some settings, symptom-free neonatal rotavirus infections are common, and provide a kind of natural ...