Addressing the vaccine confidence gap.

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.

Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices.

This report summarizes new recommendation and updates previous recommendations of the Advisory Committee on Immunization Practices (ACIP) for postexposure prophylaxis (PEP) to prevent human rabies (CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57[No. RR-3]). Previously, ACIP recommended a 5-dose rabies vaccination regimen with human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV). These new recommendations reduce the number of vaccine doses to four. The reduction in doses recommended for PEP was based in part on evidence from rabies virus pathogenesis data, experimental animal work, clinical studies, and epidemiologic surveillance. These studies indicated that 4 vaccine doses in combination with rabies immune globulin (RIG) elicited adequate immune responses and that a fifth dose of vaccine did not contribute to more favorable outcomes. For persons previously unvaccinated with rabies vaccine, the reduced regimen of 4 1-mL doses of HDCV or PCECV should be administered intramuscularly. The first dose of the 4-dose course should be administered as soon as possible after exposure (day 0). Additional doses then should be administered on days 3, 7, and 14 after the first vaccination. ACIP recommendations for the use of RIG remain unchanged. For persons who previously received a complete vaccination series (pre- or postexposure prophylaxis) with a cell-culture vaccine or who previously had a documented adequate rabies virus-neutralizing antibody titer following vaccination with noncell-culture vaccine, the recommendation for a 2-dose PEP vaccination series has not changed. Similarly, the number of doses recommended for persons with altered immunocompetence has not changed; for such persons, PEP should continue to comprise a 5-dose vaccination regimen with 1 dose of RIG. Recommendations for pre-exposure prophylaxis also remain unchanged, with 3 doses of vaccine administered on days 0, 7, and 21 or 28. Prompt rabies PEP combining wound care, infiltration of RIG into and around the wound, and multiple doses of rabies cell-culture vaccine continue to be highly effective in preventing human rabies.

Large injection site reactions after a second dose of varicella vaccine.

A second dose of varicella vaccine is routinely recommended. We report 2 cases of large local reactions after receipt of a second dose of varicella vaccine administered in the thigh. The reactions resolved with symptomatic therapy. Clinicians should continue to administer the second dose of varicella vaccine, but should use the preferred site in the arm.

Polio--new challenges in 2006.

The continued progress of the Polio Eradication Program has encountered a number of hurdles in the past 2 years as virus has spread from northern Nigeria across much of central Africa and into the Middle East and as far as Indonesia. India continues to be a source of virus exportation but to a much less degree. WHO is optimistic regarding elimination of circulating virus from all of these countries in 2006 with the exception of Nigeria. Newly recognized obstacles to the eradication are the circulating vaccine-derived polioviruses (cVDPV) and those originating from immune deficient patients (iVDPV). Data are presented on the numbers and locations of cases of paralytic polio in 2004 and 2005 as reported to the WHO in early 2006. Scenarios for the maintenance of freedom from polio when/if the final cases occur are considered.

Evidence for a 4-dose vaccine schedule for human rabies post-exposure prophylaxis in previously non-vaccinated individuals.

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.

Perspective on live varicella vaccine.

The attenuation of varicella-zoster virus (VZV) by Takahashi in 1974 was a remarkable achievement. It swiftly led to development of a live vaccine against chickenpox, which was initially tested in Japan. With its successful employment in immunocompromised children to prevent morbidity and mortality due to varicella, the vaccine began to be tested in healthy children in Japan and elsewhere. In the United States, vaccine use progressed from extensive clinical trials that demonstrated safety and efficacy to universal immunization of healthy infants and children. In the past 10 years, >30 million healthy American individuals, mostly children, have been vaccinated. With increasing use of vaccine, there has been a concomitant decrease in the incidence of disease, along with decreases in hospitalizations and deaths due to VZV. To improve protection, however, a 2-dose schedule of immunization was recommended for routine use in all children by the Centers for Disease Control and Prevention in June 2006. At roughly the same time, licensure of the combined measles-mumps-rubella-varicella vaccine was completed, which allowed harmonization of immunization against these 4 viruses with 1 injection given twice in childhood. Concomitantly, a version of the varicella vaccine with 10 times the titer was developed for immunization of healthy individuals >60 years of age against herpes zoster (HZ). Although elimination of VZV from human populations may not yet be possible, the combined approach of immunization against both varicella in childhood and HZ in adulthood in the developed world are predicted to dramatically increase our control of this troublesome virus.

Protecting public trust in immunization.

Public trust in the safety and efficacy of vaccines is one key to the remarkable success of immunization programs within the United States and globally. Allegations of harm from vaccination have raised parental, political, and clinical anxiety to a level that now threatens the ability of children to receive timely, full immunization. Multiple factors have contributed to current concerns, including the interdependent issues of an evolving communications environment and shortfalls in structure and resources that constrain research on immunization safety (immunization-safety science). Prompt attention by public health leadership to spreading concern about the safety of immunization is essential for protecting deserved public trust in immunization.

Safety concerns regarding combination vaccines. Perspective of select European countries.

This study explored health officials' perception of parental concern regarding the safety of combination vaccines and its impact on policy decisions in different European countries. Interviews were conducted with governmental and nongovernmental health officials in the United Kingdom, France, Ireland and Sweden over a four-month period. Parental concern regarding the safety of combination vaccines was perceived to be prevalent in the United Kingdom, Ireland and Sweden while no such concern was evident in France. The concern was limited to the combined measles, mumps and rubella vaccine and its alleged causal association with autism and did not carry over to other combined vaccines. Although proposed by certain political groups, no policy changes regarding combination vaccines were made in any study country.

Childhood vaccine development: an overview.

Vaccines against childhood diseases represent some of the most important applications of 20th-century pediatric research. This survey examines how the components of the current U.S. immunization schedule emerged in three phases during the course of the century. The first phase, after the development of bacterial culture techniques, witnessed numerous efforts in the early 1900s to develop bacterial vaccines. It proved most fruitful with respect to diphtheria, tetanus, and pertussis. The rise of viral tissue culture techniques in the 1950s brought about a second phase of innovation resulting in vaccines against polio, measles, mumps, rubella, and varicella. A third wave of innovation, still very much alive, has drawn on a variety of new technologies and led to vaccines against hepatitis B, Haemophilus influenzae type b, pneumococcus, and still other organisms. Although basic science research has thus been a primary factor shaping the history of vaccine development, the collaboration between the academic, private, and public sectors critical to its application has not always proceeded smoothly. The history of vaccine research and development has important implications for today, as a variety of factors threaten to fragment this network.