Second to clean drinking water, vaccination has become the most effective public health measure for the control of infectious diseases. The successful eradication of smallpox 3 decades ago naturally led to the optimistic view that childhood diseases could also be eradicated by vaccination. Indeed, there is good hope that some infectious diseases, e.g., polio and measles, may soon be eradicated. On the other hand, there are still some 3 million people, mostly infants and children ! 5 years of age living in developing countries, that die each year from diseases that are preventable by vaccines. This frustration must be balanced against the fact that new vaccines are continuously being developed and proven safe and are used with high efficacy in high-income countries. Disappointingly, we have also learned that experiences from high-income countries may not necessarily be directly applicable to low-income countries. The vaccines most needed are partly different, immune responses may vary and monetary resources and infrastructure are substantial obstacles for the implementation of the vaccine programs needed. For these reasons, this issue of Annales Nestlé is devoted to vaccines in a broader sense and using a global perspective.
Vaccination has become the most effective public health measure for the control of infectious diseases after the provision of clean drinking water. The history of vaccination is marked with great hopes and some disappointments. In particular, the second half of the 20th century witnessed the development of remarkable vaccination projects. There is a possibility that polio and measles may be eradicated within a few years, but almost 3 million people – usually children ! 5 years of age – die each year from diseases that are preventable by vaccines. Developing countries are struggling to get the vaccines to children who desperately need them. However, in Europe and North America, people have become complacent about vaccines: ‘these diseases are no longer a threat and the vaccine is more dangerous than the disease’. Those misconceptions have caused outbreaks of measles, diphtheria and pertussis. The international community must continue to devote the necessary resources, money and manpower to fully exploit the promise that vaccines hold for the relief of human misery.
Oral vaccines which are intended for global use do not necessarily induce the same immune responses in all children worldwide. In fact, several vaccines often induce less frequent and lower mean antibody responses in children in developing countries, suggesting that the vaccines may be less protective among children in these areas. Though the reasons for this less vigorous response are not completely understood, it appears that nutrition-related factors, including both protein-calorie and micronutrient malnutrition, are important aspects in understanding the hyporesponsiveness seen in these children. Related issues including breastfeeding, interference from maternal placental antibodies, intestinal parasitic infections, intestinal mucosal damage and possibly maternal malnutrition during pregnancy also appear to be important. Vaccines designed for oral administration will need to be adjusted to these potential problems in order to maximize benefits for all children. Oral vaccines, when given to children in developing countries, may require higher doses of vaccine, booster doses, calorie, micronutrient and vitamin supplements, withdrawal of breast milk before vaccine administration, deworming medications or other measures to realize their full benefit.
Introduction of new vaccines into affluent countries has occurred at a breathtaking pace in recent years. By comparison, few new-generation vaccines have been introduced into public health programs for the poor in developing countries, and, for those that have, introduction has been painfully slow. Limited financial resources have retarded the introduction. However, the slow pace also stems from a dearth of evidence needed for rational policy decisions. Inadequate support to conduct phase 1 studies of vaccine candidates targeted against diseases of developing countries is a wellknown obstacle. Additionally, other types of translational research are needed to generate the necessary evidence for policy. Many vaccines have been shown to perform less well in impoverished populations in the developing world than in persons residing in more affluent countries. Consequently, phase 2 and phase 3 trials are a second essential type of translational research needed for the introduction of vaccines in developing countries. Moreover, even for vaccines that achieve licensure via clinical trials in developing countries, doubts may remain about whether the burden of disease warrants vaccine introduction, whether the administration of the vaccine in public health programs will be cost-effective, whether vaccine introduction will be programmatically feasible and acceptable, and whether the introduction of the vaccine will be financially sustainable. To address these residual doubts, a third type of translational research is needed. Since its inception in 1987, the International Vaccine Institute, an international, non-profit research and development organization located in Seoul, Korea, has conducted translational research on new vaccine introduction for a variety of diseases in 22 countries in Asia, Africa and Latin America. In this paper, we describe translational research projects undertaken by the International Vaccine Institute and lessons learned about strategies to increase the impact of translational research on vaccine policy for the developing world.
Recent examples of the major public health benefits of vaccination include global reductions in measles mortality and record low levels of vaccine-preventable diseases in the United States. Nevertheless, real or perceived vaccine safety issues may adversely impact vaccine programs. Robust postlicensure safety monitoring which combines active and passive surveillance with use of standardized case definitions for adverse events is the scientific basis for assessing safety concerns. Emerging aspects of vaccine safety science include clinical research networks and vaccine risk communication research. Current high-profile safety issues include the introduction of 2 second-generation rotavirus vaccines, for which close monitoring of intussusception is necessary. To date, data from the US do not indicate an elevated risk associated with the licensed Merck vaccine (Rotateq ). An issue of global interest is the use of thimerosal as a preservative in multi-dose vaccine vials. Comprehensive independent reviews as well as recently published research have reaffirmed the lack of association between thimerosal and neurodevelopmental disorders, including autism. Expanded use of annual influenza vaccine and pandemic planning in the developed or developing world should include plans for safety monitoring. As the number of newly licensed vaccines increases, potentially preventable vaccine administration errors and post-vaccination events such as syncope are being increasingly recognized. Primary care clinicians and others involved in giving vaccines should follow proper vaccine storage, handling and administration procedures and should participate in adverse event following immunization (AEFI) reporting systems. The Brighton Collaboration provides another outlet, which interested clinicians and researchers can participate in, increasing the global vaccine safety knowledge base. Increased knowledge of and participation in vaccine safety systems at all levels of health care systems in both developed and developing country settings will allow vaccines to maintain their excellent safety track record, as safety data is used to improve immunization practice.