Samuel L. Katz

Addressing the vaccine confidence gap.

Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK (H J Larson PhD); Department of Paediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA (Prof L Z Cooper MD); National Institute for Health and Welfare (THL), Helsinki, Finland (J Eskola MD); Department of Paediatrics, Duke University, Durham, NC, USA (Prof S L Katz MD); Government Aff airs and Policy, Johnson & Johnson, New Brunswick, NJ, USA; (S Ratzan MD); and Journal New Decade of Vaccines 5Vaccines--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.

Persistent and fatal central-nervous-system echovirus infections in patients with agammaglobulinemia.

We observed persistent ECHOvirus infection of the central nervous system, as defined by continued presence of isolatable virus in cerebrospinal fluid, in five patients with agammaglobulinemia. The immunologic deficit in each was characterized by absence of surface-immunoglobulin-bearing B lymphocytes and of lymph-node cortical follicles, but normal T-cell function. ECHOviruses 30, 19, 9 and 33 were recovered from cerebrospinal fluid for periods varying from two months to three years. The patients had few signs of acute central-nervous-system infection. Three of the five patients had a dermatomyositis-like syndrome, with peripheral lymphocytes that reacted with anti-human leukemia-specific primate and rabbit serums in a cytotoxicity assay. These data suggest that intact B-cell function is essential for eradication of ECHOvirus infection of the central nervous system.

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.

Isolation of Measles Virus from Urine

THE etiologic agent has reportedly been recovered from the urine of patients with a number of different viral infections (rabies,1 lymphocytic choriomeningitis,2 Russian spring-summer encephalitis,...

The Unfinished Measles Immunization Agenda

Despite achieving and sustaining global measles vaccination coverage of about 80% over the past decade, worldwide measles remains the fifth leading cause of mortality among children aged <5 years. In May 2002, the United Nations Special Session on Children endorsed the goal of reducing measles deaths by half by 2005. Countries and World Health Organization (WHO) regions that adopted aggressive measles control or elimination strategies have shown excellent results. In 2001, countries in the Americas reported an all time low of 537 confirmed measles cases. Substantial progress in measles control has also been achieved in the WHO Western Pacific Region, in seven southern African countries, and in selected countries in WHO European, Eastern Mediterranean, and Southeast Asian regions. The ongoing measles disease burden and availability of safe and effective measles mortality reduction strategies make a compelling case to complete the unfinished agenda of measles immunization.

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.

Effect of influenza immunization on immunologic and virologic characteristics of pediatric patients infected with human immunodeficiency virus

OBJECTIVES We evaluated the responses of HIV-infected children to a single dose of split-virus influenza vaccine and the relationship to viral load and other characteristics. METHODS Fifty-three HIV-infected children ages 1.8 to 13.2 years were given influenza vaccine for the 1994 to 1995 influenza season (Wyeth-Ayerst: A/Texas H1N1, A/Shangdong H3N2 and B/Panama). Immunologic and virologic factors were assessed at the time of and 2 to 10 weeks after immunization. RESULTS The differences between pre- and postimmunization CD4+ counts, CD4+:CD8+ ratios and viral load were not significant. Thirty-one of 53 children (58.4%) had a > 2-fold increase and 16 of 53 (30%) had a 4-fold rise in their postimmunization antibody titers for at least one component of the vaccine. Influenza immunization in the 1993 to 1994 flu season and administration of intravenous immunoglobulin around the time of immunization was not associated with immune response to the vaccine. Factors that were negatively associated with antibody response included increased time between samples (P = 0.004) and decreased preimmunization CD4+:CD8+ ratio (P = 0.02). CONCLUSIONS Influenza immunization in this population is safe, and a positive antibody response to influenza immunization is not associated with significant clinical events or change in HIV-1 plasma viral burden.

Evaluation of surrogate markers and clinical outcomes in two-year follow-up of eighty-six human immunodeficiency virus-infected pediatric patients

OBJECTIVES To evaluate the prognostic value of surrogate markers (HIV RNA copy number, CD4 counts and CDC clinical and immunologic categories) in HIV-infected children through a 2-year period. METHODS Eighty-six HIV-infected children followed by the Duke Pediatric HIV Clinic in the fall of 1994 were evaluated for plasma HIV RNA concentration (viral load), CD4 lymphocyte percentage, age, antiretroviral treatment status and CDC clinical and immunologic categories. Follow-up evaluations were performed for approximately 2 years, and the time to progression to a new CDC category C diagnosis or death was noted. RESULTS Of 86 children 22 had progression to new Category C diagnosis or death. Seven children died, 17 had a new Category C diagnosis and 2 had both. Among children who progressed, the median CD4 percentage at entry was 3% (absolute count, 75 cells/mm3), whereas children who had no disease progression entered with a median of 29% (868 cells/mm3). The overall median viral load at study entry was 4.58 log10 copies/ml (38,019 copies/ml, with a range of 1.7 to 6.78 logs). Children who had no disease progression had a median log copy number of 4.43, whereas 5.18 was the median for children whose disease progressed. Log copy number declined over time in children < 3 years of age, whereas it remained fairly consistent for children 3 years or older. Progression rates were determined by entry plasma HIV RNA concentration quartiles [quartile boundaries < 4.18, 4.58, > 5.08 log RNA copy/ml (< 15,136, 38,019 and > 120,226 copies/ml, respectively)]. Progression rates by quartile were 0 of 21, 4 of 22, 5 of 21 and 13 of 22. Kaplan-Meier survival curves defined by CD4% less than or greater than 15 and log RNA less than or greater than 5.0 (100,000) revealed that patients with CD4% less than 15 and plasma HIV RNA concentration > 5 log10 copies/ml did least well: 11 of 12 (92%) had a progression event at a median of 179 days. Patients with a high CD4 percentage and high viral load, or a low CD4 percentage and low viral load did similarly; 5 of 14 (36%) and 4 of 12 (33%) had progression events, respectively. Patients with high CD4 percentage and low viral load did best: only 2 of 48 (4%) had a progression event. CONCLUSIONS The two most significant prognostic indicators of disease progression were the initial CD4 percentage and the plasma HIV RNA concentration, and a combination of CD4 percentage and virus load best predicted which children had progression events. Progression was less common in children who had < 100,000 HIV RNA copies/ml initially (6 of 60 vs. 16 of 26; P < 0.001; relative risk 0.16). Therefore it seems reasonable that in a child for whom complete suppression is not possible, a threshold of 100,000 (5 log10 copies/ml) can be used to mandate a change in therapy.

Immunisation against poliomyelitis: moving forward.

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.

Genotyping of Measles Virus in Canada: 1979-2002

Genotyping is an important component of measles surveillance. In this study, we report the genotypes of 30 measles viruses from cases in Canada; 6 of these were collected between 1979 and 1996 and 24 were collected from 1997 through 2002. Many measles virus genotypes were found (C1, C2, D3, D4, D5, D6, D7, D8, E, and H1). These data indicate that the predominant measles virus genotypes detected from 1979 to 1997 in Canada are no longer commonly found. Since the implementation of a routine second dose of measles vaccine and catch-up campaigns in 1996-1997, the wide variety of measles virus genotypes found supports epidemiological data showing that importation of measles is the source of current measles cases in Canada.