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Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines.

After exposure, human rabies is preventable by prompt application of post-exposure prophylaxis. Historically, the total number of rabies vaccine doses administered during human prophylaxis has decreased, as modern biologics have improved and scientific knowledge has grown. A review of the literature on rabies virus pathogenesis, experimental animal studies, clinical trials, epidemiological surveillance, and economic analyses was conducted to determine the potential utility of reducing the current 5-dose intramuscular series of human rabies vaccine administered in the United States. Based upon the available evidence, a reduced schedule of cell-culture rabies vaccine, administered on days 0, 3, 7, and 14, given in conjunction with rabies immune globulin, was supported and recommended by the United States Advisory Committee on Immunization Practices.

Increased societal concern regarding the safety of vaccines has had an impact on the risk tolerance of public health officials, parents, and medical professionals. Risks that were either unknown or accepted for years have come under new scrutiny and may result in new and changed perspectives. This has been due partly to the fact that effective immunization programs have markedly diminished the incidence of vaccine-preventable diseases in industrialized countries. As a result, there is a lower awareness of the risks associated with the diseases themselves and a greater prominence of the potential risks of adverse effects associated with the vaccines. Risk perceptions and the actions taken in response to real or perceived risks regarding vaccines can and do vary significantly among nations. Due to the heightened awareness and concern over vaccine safety issues, immunization policymakers must carefully balance newly identified potential risks from vaccines with the actual risk of vaccine-preventable diseases. Concern regarding public reactions to new and often unverified safety issues may place pressure on policymakers and/or health care providers to act quickly in response to new

9,10 The use of IPV in combination with OPV in infants could help close the immunity gap in this critically important age cohort, and tip the balance to eliminate wild poliovirus circulation. The initial reasons for the choice of OPV were its low cost, ease of administration, and its ability to induce herd immunity by person-to-person transfer. Data from developed countries suggest that IPV also has a herd eff ect, resulting from decreased transmission of wild virus to unvaccinated individuals when some of the population is immunised. Further studies are needed to determine how well IPV can reduce transmission in tropical settings and to assess its ability to stop wild poliovirus transmission and control outbreaks in the post-eradication era. Although OPV has been the mainstay of the eradication programme, its continued use is ironically incompatible with the eradication of paralytic disease. Neurovirulent vaccine-derived polioviruses (VDPVs) generated by reversion or recombination of OPV strains can circulate in poorly immunised populations and cause outbreaks of paralytic disease.

Advances in medical biotechnology mean that vaccines to prevent more than 75 infectious diseases are being or have been developed. Vaccination is unfortunately not reliant purely on biotechnology but also on politics and resources. Countries with the greatest demand for vaccines have the least ability to pay for or produce them. Health-care Infrastructure and diagnostic facilities also hamper immunisation projects in developing countries. Charitable organisations are relied on heavily to support such projects but the challenge to ensure all infants are immunised against the most common infections of childhood is still enormous. Difficulties that present themselves now should not prevent us looking into future possibilities such as immunisation during pregnancy and targeting of children for immunisation against sexually transmitted diseases. Other avenues for research are in administration of vaccines. A move to mucosal immunisation rather than use of the syringe and needle would be positive both economically and from the point of view of risk of needle contamination. Plant science may also provide a new vehicle for vaccines by engineering plants such as the banana tree to be naturally bioencapsulated vaccines. Prospects for control and eradication of infectious disease in the next century are certainly good.

Recent studies of the effects of 5-bromo- and 5-fluoro-2′-deoxyuridine demonstrated that these compounds interfered with both normal deoxyribonucleic acid (DNA) synthesis as well as viral DNA synthesis in animal and bacterial cells (1, 2, 3). A third member of this same series, 5-iodo-2′-deoxyuridine (IDU) was subsequently found to be an effective inhibitor in vitro of 2 DNA viruses, vaccinia and herpes simplex (4). With this background, Kaufman et al (5) reported in 1962 that when a supersaturated aqueous solution of IDU was placed every two hours in the conjunctival sac of humans and rabbits with herpes simplex keratitis, the viral infection subsided markedly within two days.